Search

Purpose of review Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected 'off label' as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies. Recent findings A few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group. Summary We will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.

PURPOSE OF REVIEW Universally lowering blood pressure (BP) may adversely affect some populations especially in the older population. Recent landmark trials revealed cardiovascular benefits of tight controlling systolic BP (SBP) more than several recent BP targets. Implementing the evidence from the studies and guidelines in some populations is reviewed. RECENT FINDINGS Eighth Joint National Commission (JNC-8) on hypertension issued conservative guidelines that provided an evolutionary change to BPcontrol in the elderly. However, intensive BP control with SBP

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Purpose of review Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the novel virus responsible for the current worldwide pandemic. The scientific and healthcare communities have made every effort to discover and implement treatment options at a historic pace. Patients with kidney disease are uniquely vulnerable to an infectious pandemic because of their need to be in frequent contact with the healthcare system for life-sustaining renal replacement therapy whether it be by dialysis or transplant. Recent findings The use of targeted viral therapies, extracorporeal therapies, immunosuppressive therapy and public health interventions are important in the management of patients with COVID-19 but require special consideration in patients with kidney disease because of the complexity of their condition. Summary Here, we discuss some of the major efforts made to prevent spread and emerging treatment options for this virus, as they pertain to patients with kidney disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.

PURPOSE OF REVIEW: Despite improvement in short-term renal allograft survival in recent years, renal transplant recipients (RTR) have poorer long-term allograft outcomes. Allograft function slowly declines with periods of stable function similar to natural progression of chronic kidney disease (CKD) in non-transplant population. Nearly all RTR transitions to failing renal allograft (FRG) period and require transition to dialysis. Conservative CKD management before transition to end-stage renal disease (ESRD) is an increasingly important topic; however, there is limited data in RTR regarding how to delay dialysis initiation with conservative management. RECENT FINDINGS: Since immunological and non-immunological factors unique to RTR contribute to decline in allograft function, therapies to slow progression of FRG should take both sets of factors into account. Renal replacement therapy (RRT) either incremental dialysis or re-kidney transplantation should be explored. This required taking benefits and risks of continuing immunosuppressive medications into account when allograft nephrectomy may be necessary. SUMMARY: FRG may benefit from various interventions to slow progression of worsening allograft function. Until there are stronger evidence to guide interventions to preserve renal function, extrapolating evidence from non-transplant patients and clinical judgement are necessary. The goal is to provide individualized care for conservative management of RTR with FRG.

Objective: We sought to create a classification system for pediatric corpus callosal abnormalities (CCA) based upon midline sagittal brain MRI. We used the term CCA for patients with structural variants of the corpus callosum, excluding patients with interhemispheric cyst variant or pure dysplasia without hypoplasia. Currently, no system exists for nonsyndromic forms of CCA, and attempts to create such a system have been hampered by highly variable morphology in patients with sporadic CCA. We reasoned that any useful strategy should classify affected family members within the same type, and that phenotypic variability should be minimized in patients with recessive disease. Methods: We focused recruitment toward multiplex consanguineous families, ascertained 30 patients from 19 consanguineous families, and analyzed clinical features together with brain imaging. Results: We identified 3 major CCA classes, including hypoplasia, hypoplasia with dysplasia, and complete agenesis. Affected individuals within a given multiplex family usually displayed the same variant of the class of abnormality and they always displayed the same class of abnormality within each family, or they displayed complete agenesis. The system was validated among a second cohort of 10 sporadic patients with CCA. Conclusions: The data suggest that complete agenesis may be a common end-phenotype, and implicate multiple overlapping pathways in the etiology of CCA.

PURPOSE OF REVIEW: The novel corona virus (SARS-CoV2) has been demonstrated to cause acute kidney injury due to direct cellular toxicity as well as due to a variety of autoimmune glomerular diseases. The concept of a surge of infected patients resulting in an overwhelming number of critical patients has been a central concern in healthcare planning during the COVID-19 era. RECENT FINDINGS: One crucial question remains as to how to manage patients with end stage renal disease and acute kidney injury in case of a massive surge of critically ill infected patients. Some publications address practical and ingenious solutions for just such a surge of need for renal replacement therapy. We present a plan for using a blood pump, readily available dialysis filter, and a prefilter and postfilter replacement fluid set up. This is in conjunction with multiple intravenous pumps to develop a simple hemofiltration apparatus. SUMMARY: The current set up may be a readily available option for use in critical situations where the need for renal replacement therapy outstrips the capacity of traditional hemodialysis services in a hospital or region.

Hyperkalemia is a common finding in patients with advanced kidney disease for multiple reasons. Renin-Angiotensin-Aldosterone-System Inhibitors (RAASi) that are indicated for slowing down progression of kidney disease are often associated with hyperkalemia which becomes a limiting factor in their use and titration to the maximum dose. Having a safe, effective, tolerable, and affordable potassium binder can help optimize RAAS inhibition in the setting of kidney disease.Although sodium polystyrene sulfonate has been a mainstay of acute management of hyperkalemia for decades, evidence regarding its efficacy is limited, and its chronic use is not routinely recommended for concerns regarding toxicity. The concern of gastrointestinal (GI) adverse effects with sodium polystyrene sulfonate has spurred the development of alternatives. Sodium zirconium cyclosilicate (SZC) is a promising agent that selectively binds potassium in the gut and eliminates it, while being safe for chronic use based on 1 year of data. Even though we do not have head-to-head studies among the three currently available binders, SZC stands out in rapidity of onset and efficacy.In this review, we summarize the general management of hyperkalemia, including new agents. We review the pre-clinical and clinical data relating to sodium zirconium cyclosilicate.

Vascular endothelial growth factor (VEGF) is a vital factor needed for proper endothelial cell survival, and it is increasingly recognized as an important part of podocyte cellular physiology.1 The disruption of VEGF signaling has been known as a therapeutic target in processes that involve blood vessel proliferation (angiogenesis), and as such, systemically the drugs inhibiting VEGF function are used as anti-neoplastic anti-angiogenesis adjunctive treatments.2 The systemic effects of VEGF blockade were first realized with findings of severe hypertensive crisis (due to nitric oxide signaling depletion) and overt proteinuria. Findings of thrombotic microangiopathy (TMA), increased proteinuria, and multiple causes of nephrotic syndrome were published by many experts in the burgeoning field of onco-nephrology.2, 3 It has been notable that agents blocking mammalian target of rapamycin and the tyrosine kinase pathway (TKI) produce similar renal side effects as systemic VEGF blockade.4 Physiologically, preeclampsia demonstrated similar renal effects with soluble fms-like tyrosine kinase-1–induced depletion of VEGF.5 Intravitreal use of VEGF antagonists started off label with bevacizumab, and progressed with use of aflibercept (more potent), and ranibizumab (less potent) agents both given approval for age-related macular degeneration and diabetic retinopathy by the U.S. Food and Drug Administration.6 Intravitreal VEGF blocking agents have been shown to be absorbed,7 systemic effects, such as hypertension and renal disease, have been reported, including glomerular disease.6, 8, 9,S1–S3 We report a 96-year-old elderly woman who has been on ranibizumab, then bevacizumab, then aflibercept for progressive age-related macular degeneration since 2007. She at first had marginal amounts of proteinuria, between 2017 and 2018, the patient developed high-grade nephrotic-range proteinuria and a faster rate of progression of renal dysfunction. A renal biopsy disclosed an unexpected finding of collapsing focal and segmental sclerosis (FSGS), previously reported with systemic VEGF inhibitors and TKI.S4

Background Atypical hemolytic uremic syndrome is a rare group of disorders that have in common underlying complement amplifying conditions. These conditions can accelerate complement activation that results in a positive feedback cycle. The known triggers for complement activation can be diverse and include, infection, autoimmune disease, and malignancy. Recent reports suggest that certain autoimmune and rheumatological triggers of complement activation may result in atypical hemolytic uremic syndrome that does not resolve despite treating the underlying disorder. Specifically, patients with systemic lupus erythematosus and microangiopathic hemolysis may not respond to treatment of their underlying rheumatological trigger but responded to complement blockade. Case presentations We report two patients with inflammatory bowel disease complicated by development of atypical hemolytic uremic syndrome. In both cases, patients were on treatment for inflammatory bowel disease, that was not well controlled/flaring at the time. The first patient is a male who developed Crohn’s disease and microangiopathic hemolysis at age 5 and was treated with eculizumab successfully. Discontinuation of the medication led to multiple relapses, and the patient currently is being treated with eculizumab and has normal hematological and stable renal parameters. The second patient is a 49-year-old female with Ulcerative Colitis treated with 6-Mercaptopurine. She developed acute kidney injury and microangiopathic hemolysis. Prompt diagnosis and treatment with eculizumab resulted in the recovery of kidney injury along with a complete hematological response. Conclusions These two cases are the fifth and sixth patients to be published in the literature with atypical hemolytic uremic syndrome and inflammatory bowel disease treated with complement blockade. This confirms that C5 complement blockade is effective in treating complement mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome when it is triggered in patients with inflammatory bowel disease.

Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.

Severe vitamin B12 deficiency may present with hematologic abnormalities that mimic thrombotic microangiopathy disorders such as hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. We report a patient diagnosed with severe vitamin B12 deficiency, following termination of pregnancy for suspected preeclampsia and HELLP syndrome at 21 weeks’ gestation. When hemolysis and thrombocytopenia persisted after delivery, testing was performed to rule out other etiologies of thrombotic microangiopathy, including atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and vitamin B12 deficiency. This work-up revealed undetectable vitamin B12 levels and presence of intrinsic factor antibodies, consistent with pernicious anemia. Parenteral B12 supplementation was initiated, with subsequent improvement in hematologic parameters. Our case emphasizes the importance of screening for B12 deficiency in pregnancy, especially in at-risk women with unexplained anemia or thrombocytopenia. Moreover, providers should consider B12 deficiency and pernicious anemia in the differential diagnosis of pregnancy-associated thrombotic microangiopathy.

Mammalian target of rapamycin (mTOR) inhibitors are used in renal sparing protocols and transplant immunosuppression in patients with solid organ and stem cell transplants. They cause various side effects, including proteinuria, which is mediated by blockade of the vascular endothelial growth factor receptor pathway. There have been various reports of mTOR inhibitors causing proteinuria or worsening proteinuria form preexisting renal glomerulo-pathies. We report a 73-year old male with diabetic glomerulosclerosis, acute liver failure due to Budd-Chiari syndrome, chronic low platelets, and worsening proteinuria from 0.46 g protein/g creatinine to 2.2 g protein/g creatinine. Workup revealed no thrombotic microangiopathy through skin biopsy, and a renal biopsy confirmed only clinically suspected diabetic and hypertensive glomerulosclerosis and possible calcineurin inhibitors. On discontinuation of everolimus urine protein decreased back to 0.6 g/g creatinine. We review the mechanism of mTOR-induced proteinuria and how this may affect diabetic nephropathy secondarily. We also consider the clinical implications of this in transplant patients receiving these agents.

Transplant patients are at risk for hemodynamic injury and glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and thrombotic microangiopathy (TMA). Calcineurin inhibitors (CNI) can cause various patterns of acute kidney injury (AKI) in transplant patients and their effects must be differentiated from kidney injury due to other agents. Transplant populations are also at risk for atypical infections and malignancies. These conditions and the agents that are used to treat them can then induce their own set of glomerular diseases. We report a patient with hepatitis C who had received an orthotopic liver transplant and then developed recurrent hepatocellular carcinoma, which was treated with the oral tyrosine kinase inhibitor (TKI) sorafenib. In a manner temporally related to the initiation of the TKI, progressive AKI and high-grade rising proteinuria were noted. A biopsy disclosed FSGS and concomitant TMA. Despite the discontinuation of the TKI and high-dose steroid treatment, the patient developed end-stage renal disease and was initiated on hemodialysis. After determining the TKI as the probable culprit, as opposed to CNIs, the patient successfully received a living related renal transplant. CNIs are used to maintain renal and hepatic allografts without the development of hematuria, significant proteinuria, or significant impairment of renal function. It is noted that the pathologic phenotype observed in this case is only the second reported case of concomitant TMA and FSGS in a sorafenib-treated patient.

Cetyl Alcohol is a rare cause of acidosis if ingested in large quantities. Hyponatremia with overlapping anion gap and osmolal gap‐positive metabolic acidosis may appear to have iso‐osmolar serum. This is a case of an unusual toxic exposure.

Anemia in end-stage kidney disease (ESKD) is a complex problem involving iron metabolism, deficient erythropoiesis, and inflammatory responses due to uremia and persistence of associated middle molecule molecular toxins. With the advent of the kidney X initiative, growth of peritoneal dialysis (PD) is expected to greatly increase the number of patients on home therapies. In this chapter, the pathophysiology of anemia in ESKD is discussed in detail, and the rational basis for anemia therapy is described. The use of various agents in the treatment of anemia of ESKD is outlined. Evidence-based guidelines from the literature are also reviewed in a matter useful to the clinician. The latest developments in ESKD anemia therapy are discussed (hypoxia-inducible factor-prolyl hydroxylase inhibitors). Finally factors unique to PD are discussed to crystalize the unique challenges and opportunities inherent in treating ESKD-associated anemia in PD patients.

Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1–3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.

Anemia is a frequent comorbidity of chronic kidney disease (CKD) and is associated with a considerable burden because of decreased patient health-related quality of life and increased healthcare resource utilization. Based on observational data, anemia is associated with an increased risk of CKD progression, cardiovascular events, and all-cause mortality. The current standard of care includes oral or intravenous iron supplementation, erythropoiesis-stimulating agents, and red blood cell transfusion. However, each of these therapies has its own set of population-specific patient concerns, including increased risk of cardiovascular disease, thrombosis, and mortality. Patients receiving dialysis or those who have concurrent diabetes or high blood pressure may be at greater risk of developing these complications. In particular, treatment with high doses of erythropoiesis-stimulating agents has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Resistance to erythropoiesis-stimulating agents remains a therapeutic challenge in a subset of patients. Hypoxia-inducible factor transcription factors, which regulate several genes involved in erythropoiesis and iron metabolism, can be stabilized by a new class of drugs that act as inhibitors of hypoxia-inducible factor prolyl-hydroxylase enzymes to promote erythropoiesis and elevate hemoglobin levels. Here, we review the burden of anemia of chronic kidney disease, the shortcomings of current standard of care, and the potential practical advantages of hypoxia-inducible factor prolyl-hydroxylase inhibitors in the treatment of patients with anemia of CKD.

Home dialysis is the wave of the future, and the current shift from in-center to home dialysis has been sped up by recent legislation and expert body guidance. Peritoneal dialysis (PD) comes with many physiologic, medical, psychosocial, and lifestyle benefits but with challenges in recruitment and retention as well. The keys to building an effective PD program start with an up-to-date and passionate physician champion of PD and a dedicated team. Education of chronic kidney disease (CKD) patients as they approach stages IV and V is integral in helping recruit patients appropriately. Support of the PD catheter placement team and planning ahead are important to prevent crash hemodialysis starts and to work toward urgent start PD (Abdel-Aal AK, Dybbro P, Hathaway P, Guest S, Neuwirth M, Krishnamurthy V, Perit Dial Int 34:481–493, 2014). Both core and extended teams are vital to create an integrated dialysis network, and as such we review the “team” concept in this chapter. During the Coronavirus-19 (COVID 19) era, the benefits of home dialysis, especially PD, are starting to mandate a paradigm shift in the delivery of care to ESKD patients, and those systems that are most prepared stand to reap the rewards.

Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.

Idiopathic nodular glomerulosclerosis is an unusual histopathological finding that has commonly been observed in male smokers with hypertension. It has remained an enigmatic condition and is best described as a diabetic pattern of glomerular injury seen in non-diabetic patients. It is also one of the few nicotine (smoking)-associated/smoking-associated patterns of renal injury. We present an even more unusual manifestation of this pathological finding in a 59-year-old Hispanic female who presented with chronic kidney disease approaching need for renal replacement therapy. The patient had idiopathic nodular glomerulosclerosis on kidney biopsy, despite no prior history of diabetes, nor smoking history, including no secondhand smoking exposure. The patient did have hypertension. The renal biopsy also showed evidence of chronic thrombotic-microangiopathic changes within arteries and arterioles. Genetic testing of the alternative pathway revealed an unusual and likely pathological variant of thrombomodulin supporting complement dysfunction as having a role in the presentation.

The prevalence of normoalbuminuric diabetic kidney disease (DKD) has increased in the past 20 years in the U.S. While previous studies reported the significance of nonalbuminurics pathway to kidney function loss in DKD, the factors associated with the nonalbuminuric kidney function decline remains to be elucidated. This study aimed to compare the CKD risk factors between nonalbuminuric and albuminuric DKD. Among NHANES participants (1999-2016) with diagnosed diabetes and reduced eGFR (< 60), we compared CKD risk factors (including demographics and CKD diagnosis status) between patients with normoalbuminuria (ACR Disclosure M. Mosslemi: None. R.M. Hanna: None. C. Rhee: Research Support; Self; Dexcom, Inc. K. Kalantar-Zadeh: None. E. Streja: None.

C3 dominant immunofluorescence staining is present in a subset of patients with idiopathic immune complex membranoproliferative glomerulonephritis (iMPGN). It is increasingly recognized that iMPGN may be complement driven, as are cases of "typical" C3 glomerulopathy (C3G). In both iMPGN and C3G, a frequent membranoproliferative pattern of glomerular injury may indicate common pathogenic mechanisms via complement activation and endothelial cell damage. Dysregulation of the alternative complement pathway and mutations in certain regulatory factors are highly implicated in C3 glomerulopathy (which encompasses C3 glomerulonephritis, dense deposit disease, and cases of C3 dominant MPGN). We report three cases that demonstrate that an initial biopsy diagnosis of iMPGN does not exclude complement alterations similar to the ones observed in patients with a diagnosis of C3G. The first patient is a 39-year-old woman with iMPGN and C3 dominant staining, with persistently low C3 levels throughout her course. The second case is a 22-year-old woman with elevated anti-factor H antibodies and C3 dominant iMPGN findings on biopsy. The third case is a 25-year-old woman with C3 dominant iMPGN, dense deposit disease, and a crescentic glomerulonephritis on biopsy. We present the varied phenotypic variations of C3 dominant MPGN and review clinical course, complement profiles, genetic testing, treatment course, and peri-transplantation plans. Testing for complement involvement in iMPGN is important given emerging treatment options and transplant planning.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Amyloidosis has traditionally been of a few defined varieties, most commonly including light-chain amyloidosis (AL amyloidosis) and secondary amyloidosis due to chronic inflammation (AA amyloidosis). Apolipoprotein A-I/A-II cystatin C, gelsolin, lysozyme, fibrinogen alpha chain, beta 2 microglobulin, and transthyretin familial amyloidosis represent rarer but reported varieties. Ten years ago, the first reports linked leukocyte chemotactic factor 2 (LECT2) amyloidosis as a pathological agent identified as a novel class of amyloid-generating protein. Epidemiology suggested that this was a new cause of amyloidosis that is especially common in Hispanic patients and somewhat common among patients from the Middle East-North Africa (MENA) region. We report a case of splenic and renal LECT 2 amyloidosis in a 62-year- old Hispanic male with diabetes mellitus. After an unremarkable serological workup, LECT 2 amyloidosis was diagnosed on renal biopsy. The case presentation is reviewed as a typical presentation, and the literature is reviewed regarding this newly reported entity, resulting in infiltrative renal amyloidosis and chronic renal disease.

INTRODUCTION Erythropoietin stimulating agents (ESA) hyporesposiveness has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of decline of residual kidney function (RKF) on ESA hyporesposiveness has not been adequately elucidated among patients receiving HD. METHODS The associations of RKF decline with erythropoietin resistance index (ERI; average weekly ESA dose [units])/post-dialysis body weight [kg]/hemoglobin [g/dL]) were retrospectively examined across four strata of annual change in RKF (residual renal urea clearance [KRU]

Certain diabetic and hypertensive patients started on intravitreal vascular endothelial growth factor inhibition for diabetic retinopathy may experience worsening of hypertension and proteinuria. The etiology of this is the newly recognized absorption of intravitreally injected vascular endothelial growth factor inhibitors, and the susceptibility of patients with pre-existing renal disease to exacerbations depends on the degree of systemic absorption. There are eighteen reported cases of worsening hypertension, woresening proteinuria, worsening renal function, thrombotic microangiopathy, and glomerular disease noted after initiation of intravitreal vascular endothelial growth factor blockade. This nineteenth case demonstrates worsening hypertension and proteinuria with the start of bevacizumab. Both blood pressure and proteinuria parameters showed overall improvement with switching to the less absorbed and lower potency agent ranibizumab. There was a slight rise in serum creatinine after bevacizumab therapy, which stabilized at a new baseline, and the serum creatinine remained stable on ranibizumab. There were no other nephrotoxic exposures that explained the mild rise in serum creatinine. Because of improvement in renal function and proteinuria, a renal biopsy was deferred for the time. This case re-demonstrates the risk of worsening proteinuria with vascular endothelial growth factor inhibitors when given intravitreally in some patients. The demonstration of improvement in blood pressure and proteinuria with the use of lower potency agents like ranibizumab is novel and an important concept confirming observations from pharmacokinetic studies. The switch to ranibizumab offers a therapeutic option when proteinuria worsens with intravitreal vascular endothelial growth factor blockade, and the patient requires ongoing intravitreal therapy for treatment of diabetic retinopathy.

Rationale & Objective Euvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia. However, a recent observational study suggested an elevated risk for serum sodium level overcorrection with 15 mg of tolvaptan in patients with SIADH. Study Design A retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan. Settings & Participants Patients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared with patients using a 15-mg dose from patient-level data from the observational study described previously. Predictors Tolvaptan dose of 7.5 versus 15 mg daily. Outcomes Appropriate response to tolvaptan, defined as an initial increase in serum sodium level > 3 mEq/L, and overcorrection of serum sodium level (>8 mEq/L per day, and >10 mEq/L per day in sensitivity analyses). Analytical Approach Descriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test). Results Among 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L per day and 2 (11.1%) patients corrected their serum sodium levels by >8 mEq/L per day, with 1 of these increasing by >12 mEq/L per day. Of those receiving tolvaptan 7.5 mg, 14 had efficacy, with increases ≥ 3 mEq/L; similar results were seen with the 15-mg dose (21 of 28). There was a statistically significant higher chance of overcorrection with the use of 15 versus 7.5 mg of tolvaptan (11 of 28 vs 2 of 18; P = 0.05; and 10 of 28 vs 1 of 18; P = 0.03, for >8 mEq/L per day and >10 mEq/L per day, respectively). Limitations Small sample size, retrospective, and nonrandomized. Conclusions Tolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan., Graphical abstract

Hypercalcemia is a common electrolyte disorder and is typically caused by parathyroid-dependent and parathyroid-independent causes. The most common parathyroid-independent causes include malignancy, granulomatous diseases, over-supplementation with calcium, and hypervitaminosis D. We present an unusual case of a woman who had Stimulan implanted after an artificial knee joint infection. When a washout was done, the patient's serum calcium started rising, peaking at an astounding 21.2 mg/dL (normal range 8.4 - 10.2 mg/dL) with acute kidney injury. After aggressive hydration and treatment with furosemide, bisphosphonates, and calcitonin, the serum calcium dropped to 10.1 mg/dL. A full hypercalcemia workup did not reveal an alternate cause. On further investigation, it was found that Stimulan is calcium based, and the agitation of these beads during washout was hypothesized to result in the observed profound hypercalcemia.

Scleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots. The patient’s scleroderma renal crisis was severe, progressive, and refractory to the standard of care therapy: oral captopril. Biopsy showed a diffuse thrombotic microangiopathy and findings consistent with scleroderma renal crisis. We hypothesize that depletion of systemic vascular endothelial growth factor with intravitreal anti–vascular endothelial growth factor injections likely contributed to the particularly severe presentation seen in this case. Though the finding of a monoclonal gammopathy of undetermined significance is another complicating factor, this case suggests that vascular endothelial growth factor inhibition may be a newly recognized trigger of scleroderma renal crisis.

Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation. It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients. Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation. Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation. Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation. During late post-transplant period, chronic renal allograft dysfunction becomes an additional cause of hypertension. As these patients develop more substantial chronic kidney disease affecting their allografts, fibroblast growth factor 23 (FGF23) increases and is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients. The exact relationship between increased FGF23 and post-transplant hypertension remains poorly understood. Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment and should be individualized. Until strong evidence in the kidney transplant population exists, a BP of

Circulating antineutrophil cytoplasmic antibodies (ANCAs) are the central pathogenic mechanism for a group of systemic and renal syndromes called the ANCA-associated vasculitis (AAV). The nomenclature has changed from eponymous labeling to granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. These syndromes predominantly affect the pulmonary and renal systems. We also review the molecular pathology behind ANCAs and associated antigens and infections. Various clinical presentations, the multiple target organs affected, and diagnostic challenges involved in identifying these diseases are discussed. Treatment updates are also provided with regard to new studies and the now standard use of anti-CD-20 monoclonal antibodies as first-line therapy in all but the most aggressive presentations of this disease. Maintenance regimens and monitoring strategies for relapse of vasculitis and associated systemic complications are discussed.

Sarcoidosis is a rare autoimmune disease resulting in formation of non-necrotizing “non-caseating” granulomas generally in the lung. The disease classically strikes African American females in their fourth and fifth decades. The resulting hypercalcemia is a result of 1-α hydroxylase overexpression in granulomas with increased 1,25-dihydroxy vitamin D levels. This phenomenon can also be observed in mycobacterial and fungal infections that produce granulomas in infected patients. Thus, chronic infectious diseases are part of differential diagnosis of granulomatous processes. We present an elderly Caucasian female who presented with hypercalcemia with serum calcium of 11 – 14 mg/dL and an elevated ionized calcium of 1.4 – 1.5 mmol/L. Initially cholecalciferol supplements were stopped, but hypercalcemia persisted for more than 2 months. 1,25-dihydroxy vitamin D levels were markedly elevated with low normal 25-hydroxy vitamin D levels, angiotensin-converting enzyme levels were also high, and chest computed tomography (CT) imaging was negative for any lymphadenopathy (including perihilar lymphadenopathy). Malignancy and infectious workups were negative for fungal and mycobacterial infections. Positron emission tomography revealed several small lymph nodes in right upper lobe of lung, and biopsy of bone marrow and lung lymph-nodes revealed non-caseating granulomata. We present an atypical case of occult sarcoidosis presenting mainly with biochemical findings without any definitive imaging findings, making diagnosis a clinical challenge.

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.

Pseudohyponatremia represents an artifactual reduction of blood (serum or plasma) sodium concentration measured with indirect ion selective electrode (ISE) methods. One mechanism of such artifacts is usually due to an abnormal increase in lipids or protein, the nonaqueous components of blood, that result in errors due to water displacement artifacts.1, 2 Other mechanisms that cause pseudohyponatremia may be associated with monoclonal proteins when a sample’s hyperviscosity causes aspiration errors.3 In classic hyperlipidemia (hypertriglyceridemia)-induced hyponatremia, several equations have been published to correct errors in serum potassium, chloride, and sodium measurements. One such equation is as follows: Corrected Na+ = Measured Na+ + [{[0.21 × triglycerides (g/l)] − 0.6} × (Na+/100)].4 Using this equation, the estimated decrease of plasma sodium concentration could be as low as 3.9 mmol/l in a sample with triglyceride concentration of 1500 mg/dl (15 g/l) and sodium concentration of 130 mmol/l. We report a case of a 41-year-old man who developed pseudohyponatremia due to hypercholesterolemia with concomitant hypertriglyceridemia and hyperglycemia. The hyponatremia was not fully accounted for by the true dilutional hyponatremia due to hyperglycemia,5 and examination of the sample revealed that hypercholesterolemia is the culprit for the pseudohyponatremia. Institutional review was not required for this study because this case study does not provide patient identification and the blood samples used in the study were obtained for patient care, not for research purposes.

Objectives Cerebrovascular disease has increasingly been linked to overall vascular health. Pathologic conditions like diabetes, hypertension, and kidney disease have been shown to affect brain health and cerebrovascular and nervous systems. Acute kidney injury (AKI) and chronic Kidney Disease (CKD) represent a variety of vascular insults that can adversely affect cerebral health. Hypertension, fluctuations in blood pressure, and diabetic vasculopathy are known risk factors for cerebrovascular disease associated with CKD. Other emerging areas of interest include endothelial dysfunction, vascular calcification due to calcium and phosphorus metabolism dysregulation, and uremic neuropathy present the next frontier of investigation in CKD and cerebrovascular health. Methods It has become apparent that the interrelation of AKI and CKD with vascular health, chemical homeostasis, and hormonal regulation upset many aspects of cerebral health and functioning. Stroke is an obvious connection, with CKD patients demonstrating a higher proclivity for cerebrovascular accidents. Cerebral bleeding risk, uremic neuropathies, sodium dysregulation with impacts on nervous system, vascular calcification, and endothelial dysfunction are the next salient areas of research that are likely to reveal key breakthroughs in renal-cerebral pathophysiology. Results In this review nephrological definition are discussed in a neuro-centric manner, and the areas of key overlap between CKD and cerebrovascular pathology are discussed. The multifaceted effects of renal function on the health of the brain are also examined. Conclusion This review article aims to create the background for ongoing and future neurological-nephrological collaboration on understanding the special challenges in caring for patients with cerebrovascular disease who also have CKD.

Advanced mechanical circulatory support is increasingly being used with more sophisticated devices that can deliver pulsatile rather than continuous flow. These devices are more portable as well, allowing patients to await cardiac transplantation in an outpatient setting. It is known that patients with renal failure are at increased risk for developing worsening acute kidney injury during implantation of a ventricular assist device (VAD) or more advanced modalities like a total artificial heart (TAH). Dealing with patients who have an implanted TAH who develop renal failure has been a challenge with the majority of such patients having to await a combined cardiac and renal transplant prior to transition to outpatient care. Protocols do exist for VAD implanted patients to be transitioned to outpatient dialysis care, but there are no reported cases of TAH patients with end stage renal disease (ESRD) being successfully transitioned to outpatient dialysis care. In this report, we identify a patient with a TAH and ESRD transitioned successfully to outpatient hemodialysis and maintained for more than 2 years, though he did not survive to transplant. It is hoped that this report will raise awareness of this possibility, and assist in the development of protocols for similar patients to be successfully transitioned to outpatient dialysis care.

Hyponatremia is a complex process caused by dysregulation of total body sodium and total body water that can be seen in hypovolemic, euvolemic, and hypervolemic states. Rapid correction of hyponatremia can also lead to serious complications. The development of V2 antagonists, such as tolvaptan, has changed and simplified the management of dilutional hyponatremia by allowing the targeting of antidiuretic hormone (ADH) action and blocking its effect on the V2 receptor. This will decrease the synthesis and relocation of aquaporin 2 to the cortical collecting duct apical membrane. Tolvaptan is approved to be used in euvolemic and hypervolemic hyponatremia, specifically in the syndrome of inappropriate antidiuretic hormone secretion and heart failure. The SALT-1 and SALT-2 studies suggested a starting dose of 15 mg of tolvaptan based on pharmacokinetic data, and while this is an effective dose, multiple studies have shown that patients can overcorrect with this starting dose. At least 1 case of osmotic demyelination – the dreaded complication of overly rapid hyponatremia correction – has been observed with tolvaptan use. While strategies for rapid attenuation of this overcorrection exist, and are discussed, starting tolvaptan at a lower dose of 7.5 mg initially and up-titrating even within the first day is another strategy that can avoid overcorrection. This was noted to be especially important in cases of hyponatremia due to the syndrome of inappropriate ADH secretion. We note that this approach can more slowly correct the hyponatremia with less attendant neurological risks than the currently recommended minimum starting dose of tolvaptan.

IntroductionThrombotic microangiopathies (TMA) can be caused by diverse clinical entities of various etiologies. Thrombotic thrombocytopenic purpura (TTP) is caused by a lack of von Willebrand-fact...

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a pulmonary-renal syndrome affecting small and medium sized blood vessels. The disease has a prevalence in studies ranging from 3 to 15.7 cases per 100,000, with a noted increasing incidence and prevalence in more recent studies. Pulmonary manifestations include hemorrhage, lung cavitary lesions, and pulmonary fibrosis. Within the kidney, GPA is known to cause rapidly progressive pauci-immune crescentic glomerulonephritis. Rare and severe cardiovascular manifestations include pericarditis, arrhythmias, myocarditis, and aortic valve disease. Our patient is a 43-year-old female with typical pulmonary and renal lesions from GPA and also acute myocarditis, multiple episodes of ventricular tachycardia, and a severe reactive thrombocytosis.

Severe heart failure is increasingly being managed by cardiac transplantation, and in some cases mechanical support devices serve as destination therapies. Left ventricular assist devices (LVADs) were approved for destination therapy for end stage heart failure patients before the more advanced total artificial heart modality became available. One common complication of mechanical assist device placement is acute kidney injury. Historically, patients with mechanical support devices have had to have inpatient hemodialysis until combined heart kidney transplant. Though, some units have started accepting LVAD patients in outpatient dialysis clinics. The cost of in center hemodialysis remains high and home dialysis modalities are becoming increasingly popular. We report the first patient with an LVAD to undergo training and successful home hemodialysis while awaiting combined heart kidney transplantation.

Objectives of Review: Protein-energy wasting (PEW) is a state of disordered catabolism resulting from metabolic and nutritional derangements in chronic disease states. Patients with chronic kidney disease (CKD), and end-stage renal disease (ESRD) in particular, have muscle wasting, sarcopenia, and cachexia that contribute to frailty and morbidity. Moreover, reverse epidemiology findings have strongly linked PEW with mortality in CKD and ESRD. Updated Findings: The malnutrition-inflammation score (KALANTAR Score) provides a useful tool to predict nutritional risk. A stronger focus on renal nutrition in renal patients is needed to attenuate cachexia and muscle loss. Malnutrition is a far greater threat in patients with renal disease than obesity, which means dietary counseling needs to be tailored to reflect this observation. The need to achieve optimal caloric intake is compounded by the need to limit excess protein intake in CKD, resulting in the need for energy supplementation to avoid PEW. Preventing PEW is the most pressing clinical concern in CKD/ESRD. Other nutritional issues to reckon in renal disease include the need to normalize serum bicarbonate to manage acidosis, uric acid control, and phosphorous control in CKD and ESRD. Exercise maybe beneficial, but further work is needed to prove a conclusive benefit via a randomized trial. Summary: PEW prevention is an integral part of renal nutrition and is of paramount importance given the obesity paradox. Integrative approaches by physicians and dieticians are needed to take a holistic view of a patient’s diet beyond just control of particular laboratory parameters.

Systemic vascular endothelial growth factor (VEGF) inhibitions can induce worsening hypertension, proteinuria and glomerular diseases of various types. These agents can also be used to treat ophthalmic diseases like proliferative diabetic retinopathy, diabetic macular edema, central retinal vein occlusion and age-related macular degeneration. Recently, pharmacokinetic studies confirmed that these agents are absorbed at levels that result in biologically significant suppression of intravascular VEGF levels. There have now been 23 other cases published that describe renal sequela of intravitreal VEGF blockade, and they unsurprisingly mirror known systemic toxicities of VEGF inhibitors. We present three cases where stable levels of proteinuria and chronic kidney disease worsened after initiation of these agents. Two of our three patients were biopsied. The first patient’s biopsy showed diabetic nephropathy and focal and segmental glomerulosclerosis (FSGS) with collapsing features and acute interstitial nephritis (AIN). The second patient’s biopsy showed AIN in a background of diabetic glomerulosclerosis. This is the second patient seen by our group, whose biopsy revealed segmental glomerulosclerosis with collapsing features in the setting of intravitreal VEGF blockade. Though FSGS with collapsing features and AIN are not the typical lesions seen with systemic VEGF blockade, they have been reported as rare case reports previously. In addition to reviewing known elements of intravitreal VEGF toxicity, the cases presented encompass renal pathology data supporting that intravitreal VEGF blockade can result in deleterious systemic and renal pathological disorders.

Ruxolitinib is a targeted agent that inhibits Janus 2 Kinase and is approved for use in Polycythemia Vera and Primary Myelofibrosis. Its mechanism of action involves inhibition of cellular proliferation via the Janus kinase/signal transducer and activator of transcription proteins pathway. Ruxolitinib has different immune modulating effects that result in functional immunosuppression, leading to an increased susceptibility to certain infections. Klebsiella pneumoniae infections, in particular, were common among the reported pathogens contracted by ruxolitinib users. We report a 75-year-old male patient who had recurrent K. pneumoniae urinary tract infections while on ruxolitinib for Polycythemia Vera. This case is reported to add to the literature describing an increased susceptibility of patients to this often-resistant bacteria and to raise awareness about the immune modulating effects of JAK inhibitors.

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease induced by many triggers, all of which produce a common end phenotype of microangiopathic hemolysis and thrombotic microangiopathy. We herein describe a 63-year-old woman with ongoing protein-losing enteropathy and frequent transudates caused by hypoalbuminemia. The patient was treated with eculizumab with a full hematologic and partial renal response. Protein-losing enteropathy is an inflammatory condition that has been linked with increased complement activation, which can trigger aHUS in patients with loss of CD55 expression. The patient in the present case had an increased estimated glomerular filtration rate but stage IV to V chronic kidney disease. One year later, she remains off dialysis with a stable estimated glomerular filtration rate. We herein report an unusual trigger of complement activation that in turn triggered aHUS in this patient.

Membranous glomerulonephritis is the most common glomerular disease in adults. Its primary form has been characterized with formation of phospholipase A2 receptor antibodies. Malignancy, infections, and autoimmune disorders are the most common causes of secondary membranous glomerulonephritis. We present a case of a 55-year-old African American female who presented with nephrotic range proteinuria and diagnosed with secondary membranous glomerulonephritis based on distinct pathological features on kidney biopsy and absence of serum phospholipase A2 receptor antibodies. She initially underwent extensive workup for malignancies, infections, and common autoimmune disorders which were all negative. Her proteinuria remained resistant to steroid treatment and she was treated with subcutaneous adrenocorticotropic hormone injections. Meanwhile, she was also diagnosed with the anti-muscle specific kinase antibody variant of myasthenia gravis. In literature, there are few case reports of myasthenia gravis as a cause of secondary membranous glomerulonephritis. In our case, the lack of other inciting factors also suggested this association.