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Introduction: Cell-based therapies potentially delay the trajectory toward end-stage kidney disease (ESKD) in late stage 4 diabetic chronic kidney disease (DKD). We describe the trial design, baseline patient characteristics, and early results of an IRB-approved phase II multicenter clinical trial, utilizing Renal Autologous Cell Therapy (REACT) in adults with pre-ESKD due to type 2 DKD. The trial objectives were safety and tolerability of REACT by assessment of the procedure, product administration, and renal-specific adverse events in addition to evaluate the impact on renal function following injection. Methods: Ten adults with an eGFR of 14–20 mL/min/1.73 m2 were enrolled in a single-arm open-label trial. Following a percutaneous kidney biopsy, an ex vivo expansion of selected renal cells that form the REACT was injected into the cortex of the biopsied kidney with CT image guidance. Each participant received two doses of the REACT product at 6-month intervals. A 6-month observation pre-trial was required to establish patients’ “own” baseline and rate of DKD progression. Results: Five men and 5 women underwent 19 REACT injections (1 participant received only one injection). Their baseline characteristics were as follows: 3 Hispanic/Latino, 7 non-Hispanic, 7 white; mean (SD) age: 58.9 years (5.22), BMI 35.8 (8.2), eGFR (sCR) 15.5 (2.72), eGFR (sCR + Cys-C) 17.7 (3.67) mL/min/1.73 m2, sCr 3.6 mg/mL (0.73), Cys-C 2.6 mg/mL (0.52), and log random UACR 7.9 mg/g (1.01). The pre- and post-injection eGFR slope was −6.5 mL/min/1.73 m2 and −3.9 mL/min/1.73 m2. No cell-related adverse events occurred, and two procedure-related hematomas required observation without transfusion or angiographic interventions. Dialysis was delayed a mean of 16 months (range 6–28 months). At 15 months, 2 patients (20%) have eGFR slope stability and have not commenced renal replacement therapy. Conclusion: Trials that include patients with an eGFR of 2 are uncommon, and none to date involve autologous homologous cell-based treatments. REACT has the potential to stabilize or delay dialysis in high-risk late stage 4 DKD.

Background Although chronic kidney disease (CKD) affects 15% of the United States (US) population, Methods Data from the 1999–2014 National Health and Nutrition Examination Survey (NHANES) were used (n = 38 474); response rate > 70%. CKD self-report and lab-confirmed CKD were used to assess CKD unawareness. Adjusted logistic regression models examined association between unawareness and patient characteristics. Results In individuals with lab-confirmed CKD (n = 7137, 14.3%), 91.5% answered ‘no’ to self-report question; in those without CKD, 1.1% answered ‘yes’ to self-report question. In those with lab-confirmed CKD, in the adjusted models, increased age [odds ratio (ORs), 1.03 (95%CI, 1.02–1.04)] and female sex [OR, 1.37 (95%CI, 1.08–1.72)] were statistically significantly associated with greater odds of being unaware of CKD. Conclusion These findings demonstrated high unawareness of disease status as there was a discrepancy between respondents’ self-reported CKD diagnosis and lab-confirmed CKD. Older individuals and women may be more unaware of their CKD; these groups should be queried about reasons for increased unawareness.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Joshua Dill,1 Billie Bixby,1 Huthayfa Ateeli,1 Benjamin Sarsah,2 Khushboo Goel,3 Ryan Buckley,3 Ilya Finkelshteyn,3 Bijin Thajudeen,2 Pradeep V Kadambi,4 Christian Bime1 1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, The University of Arizona, Tucson, AZ, USA; 2Division of Nephrology, Department of Medicine, The University of Arizona, Tucson, AZ, USA; 3General Internal Medicine, Department of Medicine, The University of Arizona, Tucson, AZ, USA; 4Department of Medicine, University of Florida College of Medicine – Jacksonville, Jacksonville, FL, USA Background: Patients with acute respiratory distress syndrome (ARDS) who develop acute kidney injury have increased mortality and frequently require renal replacement therapy (RRT). The optimal timing for initiation of RRT after onset of ARDS to improve survival is not known. Methods: We retrospectively reviewed clinical data on patients admitted to our health system over a 2-year period. Individual charts were carefully reviewed to ascertain that patients met the Berlin criteria for ARDS and to categorize RRT utilization. The Kaplan–Meier analysis was conducted to compare early (£48hours postintubation) versus late (>48hours postintubation) initiation of RRT. Associations between RRT initiation and mortality were evaluated using Cox proportional hazards regression. Results: A total of 75 patients were identified with ARDS, 95% of whom received RRT. Mortality of patients who required RRT was 56%. The main indications for RRT initiation were fluid overload (75%), metabolic acidosis (64%), and hyperkalemia (33%). The Kaplan–Meier analysis comparing early initiation of RRT to late initiation of RRT showed no survival benefit. Cox proportional hazard models testing the association between timing of RRT initiation with survival and adjusting for sex, race, ethnicity, and Acute Physiology and Chronic Health Evaluation IIscore did not reach statistical significance (HR=0.94, 95% CI=0.48–1.86). Conclusion: Timing of RRT initiation was not associated with a survival benefit. Prospective study in the utilization and outcomes of RRT in ARDS could assist in optimizing its usage in this population. Keywords: acute respiratory distress syndrome, AKI, dialysis, intensive care, renal

Rationale and Objective Kidney biopsy data inform us about pathologic processes associated with SARS CoV-2 infection. We conducted a multi-center evaluation of kidney biopsy findings in living patients to identify various kidney disease pathology in patients with COVID-19 and their association with SARS-CoV-2 infection. Study Design Case series. Setting and Participants We identified 14 native and 3 transplant kidney biopsies performed for-cause in patients with documented recent or concurrent COVID-19 infection treated at 7 large hospital systems in the United States. Observations Males and females were equally represented in our study cohort, with a higher proportion of Black (n=8) and Hispanic (n=5) patients. All 17 patients had RT-PCR confirmed COVID-19 infection, but only 3 presented with severe COVID-19 symptoms. Acute kidney injury (AKI; n=15) and proteinuria (n=11) were the most common indications for biopsy and these symptoms developed concurrently or within 1 week of COVID-19 symptoms in all patients. Acute tubular injury (n=14), collapsing glomerulopathy (n=7) and endothelial injury/thrombotic microangiopathy (n=6) were the most common histologic findings. Two of the three transplant patients developed active antibody-mediated rejection weeks after COVID-19 infection. Eight patients required dialysis, but others improved with conservative management. Limitations Small study size and short clinical follow up. Conclusions Cases of even symptomatically mild COVID-19 infection were accompanied by AKI and/or heavy proteinuria that prompted a diagnostic kidney biopsy. While acute tubular injury was seen among the majority of them, uncommon pathology such as collapsing glomerulopathy and acute endothelial injury were detected, and most of these patients progressed to irreversible kidney injury and dialysis., Acute kidney injury is common in patients with COVID-19 disease. We undertook a multi-center center study to evaluate kidney biopsy findings in living patients to identify different kidney disease pathology in COVID-19 patients. Most patients in our cohort developed acute kidney injury concurrent with mild COVID-19 symptoms. Acute kidney injury (AKI) and proteinuria were the most common indications for biopsy. Both common and rare pathological processes such as acute tubular injury, collapsing glomerulopathy, and endothelial injury/thrombotic microangiopathy were the most common histologic findings. Two of the three transplant patients developed active antibody-mediated rejection weeks after COVID-19 infection. These data suggest that even symptomatically mild COVID-19 infection can be associated with AKI and/or heavy proteinuria and may warrant diagnostic kidney biopsy.

Hyponatremia is the most frequently observed electrolyte abnormality in clinical practice, and its frequency is almost double in hospitalized cancer patients. As a subset of cancer, hyponatremia is quite common in lung cancer patients, and it is often coupled with the diagnosis of syndrome of inappropriate antidiuretic hormone secretion. The presence of hyponatremia is consequential in that its presence adversely affects cancer patients' prognosis and outcomes. Limited data suggest that correcting hyponatremia in lung cancer patients can increase response to anticancer treatment, may help reduce length of hospital stay and cost, and reduce morbidity and mortality. The type of treatment for hyponatremia depends on several factors; the key factors are the duration and severity of neurological symptoms of hyponatremia and the status of extracellular volume. When hyponatremia is caused by syndrome of inappropriate antidiuretic hormone, hypertonic saline is indicated for acute symptomatic cases, whereas fluid restriction is recommended in chronic asymptomatic hyponatremia. The latter allows a slower rate of correction, thus avoiding the dreaded complication of osmotic demyelination syndrome. Fluid restriction is, however, insufficient or impractical, and often the use of pharmacological therapy such as antidiuretic hormone receptor antagonists becomes necessary. Availability of these antagonists as an effective treatment in the management of hyponatremia has been a major breakthrough, and furthermore, its clinical or investigational use in cancer-related hyponatremia may offer a potential opportunity to gain further insights into the prognostic impact of hyponatremia correction on cancer patients' outcomes. Tolvaptan is a prototype of ADH receptor antagonists that acts at renal tubular levels to increase free water excretion without inducing major systemic electrolyte abnormalities such as hypokalemia or alkalosis. The aim of this paper is to provide a brief review while focusing on cancer hyponatremia; (1) of the epidemiology of hyponatremia and its pathophysiology and diagnostic approaches and (2) of the pharmacokinetics of tolvaptan and its clinical efficacy, safety, and compliance.

ANCA-associated vasculitis (AAV) is the most common cause of crescentic rapidly progressive glomerulonephritis (GN). Levamisole used as an adulterant in cocaine is increasingly recognized as a cause of AAV. We report the case of a 50 year old woman with atypical anti-MPO AAV associated with cocaine use and exposure to levamisole. In addition to the clinical and pathologic findings of crescentic GN, the patient also had biopsy evidence of secondary membranous nephropathy (MN). Although AAV and MN have been reported previously in the same patient and both have been induced by drug exposures, this is the first report of MN in a patient with AAV likely induced by levamisole. We suggest that MPO can cause both pauci-immune vasculitis and secondary membranous nephropathy in some cases, as in cases of levamisole-adulterated cocaine use.

Bacterial peritonitis is a common complication of peritoneal dialysis, but fungal peritonitis is unusual and is mostly due to Candida species. Peritonitis due to Histoplasma capsulatum is rare and we report one such case. A 63-year-old female presented with progressively worsening abdominal pain, fever, and altered mental status. She had end-stage renal disease and had been on peritoneal dialysis for 4 years. She had abdominal tenderness without rebound or guarding. Laboratory studies and CT of abdomen were significant for leukocytosis and peritoneal membrane thickening, respectively. Peritoneal dialysis fluid study was consistent with peritonitis and culture of the fluid grew Histoplasma capsulatum. Treatment recommendations include removal of catheter and initiation of antifungal therapy. With the availability of newer antifungals, medical management without removal of PD catheter is possible, but at the same time if there is no response to treatment within a week, PD catheter should be removed promptly.

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B‐cell‐dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

Twenty percent of patients with type-2 diabetes mellitus without albuminuria progress to chronic kidney disease (CKD). The various factors related to development of CKD, the natural course of renal dysfunction as well as mortality in this sub-group of diabetics has not been studied in detail. The medical records of 121 patients (all males) above the age of 40 years with type-2 diabetes mellitus and CKD, and without proteinuria, were reviewed in this retrospective study. The outcomes measured included: (a) all-cause mortality, (b) need for hemodialysis (HD), (c) appearance of proteinuria and (d) trend in kidney function. The all-cause mortality was 33%, with mean age at death being 75.9 years. Sixty-three percent of the patients had improvement in estimated glomerular filtration rate (eGFR) at the end of the follow-up period. The mortality was higher in patients with worsening eGFR compared with those with improvement in eGFR (61% vs 39%, P = 0.040). 5.8% of the patients ended up on HD and 16.51% developed proteinuria at the end of the follow-up period. Patients who developed proteinuria showed a higher tendency for progression of renal failure. Multivariate logistic regression for trend toward improving versus worsening of the eGFR revealed no statistically significant predictors. This observational study suggests that in type-2 diabetic patients with CKD, a substantial number of patients will have improvement in eGFR over time. Careful search for potential reversible causes of kidney damage could help in reducing mortality.

Objective: To examine whether a significant difference exists between the reported ranges of granular and muddy brown casts in urine specimens using manual microscopy compared with an automated urine analyzer in a cohort of patients with acute kidney injury (AKI). Methods: Freshly voided urine specimens from 25 consecutive patients who were under evaluation by the Department of Nephrology for AKI were simultaneously examined using the iQ200 automated microscopy system and manual microscopy performed by a trained observer. We coded the results according to the number of pathological casts identified and performed a 3 × 2 Freeman-Halton extension of the Fisher exact probability test. Results: Overall, the number of casts identified via manual microscopy differed significantly (P

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. Eculizumab, a monoclonal complement C5 antibody which prevents the induction of the terminal complement cascade, has recently emerged as a therapeutic option for aHUS. We report a case of aHUS successfully treated with eculizumab. A 51-year-old male was admitted to the hospital following a mechanical fall. His past medical history was significant for rheumatic valve disease and mitral valve replacement; he was on warfarin for anticoagulation. A computed tomography scan of the head revealed a right-sided subdural hematoma due to coagulopathy resulting from a supratherapeutic international normalized ratio (INR). Following treatment with prothrombin complex concentrate to reverse the INR, urine output dropped and his serum creatinine subsequently increased to 247.52 µmol/l from the admission value of 70.72 µmol/l. Laboratory evaluation was remarkable for hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), low haptoglobin, and low complement C3. A renal biopsy was consistent with TMA, favoring a diagnosis of aHUS. Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH. Hemodialysis was terminated after 2.5 months due to improvement in urine output and solute clearance. The interaction between thrombin and complement pathway might be responsible for the pathogenesis of aHUS in this case. Eculizumab is an effective therapeutic agent in the treatment of aHUS. Early targeting of the complement system may modify disease progression and thus treat aHUS more effectively.

Renal artery thrombosis is a rare, but serious and often under-diagnosed condition. We report a case of bilateral renal artery thrombosis secondary to acute necrotizing pancreatitis. A 66-year-old female presented with abdominal pain and acute kidney injury (AKI). A renal biopsy showed organized intraluminal thrombi and a computer tomography scan of the abdomen showed bilateral renal artery thrombosis. Emergent laprotomy showed necrosed pancreas. Doppler studies showed deep vein thrombosis of the lower extremities and internal jugular vein thrombosis. Workup for hypercoagulability was unremarkable. The final diagnosis was AKI secondary to bilateral renal artery thrombosis probably due to hypercoagulability of acute necrotizing pancreatitis.

Background: Diabetic nephropathy is the most common cause of chronic kidney disease and the number afflicted patients continues to rise. The presence of proteinuria has been considered as a prerequisite for the diagnosis of diabetic nephropathy. But one third to one half of type 2 diabetics with CKD have no proteinuria and the pathology of non proteinuric CKD in this group remains unclear as renal biopsy is commonly not performed in these patients. The present study addresses the question: Can a classical diabetic nephropathy occur in the absence of proteinuria? Method: We examined renal biopsies of subjects who underwent nephrectomy from 1999 to 2009 for renal cancer, had eGFR

Diabetes mellitus (DM) is an increasing global public health problem characterized by β-cell dysfunction and insulin resistance. The prevalence of DM is increasing worldwide due to aging populations, physical inactivity, obesity, rapid urbanization, and changing lifestyle and food consumption patterns [1]. According to the International Diabetes Federation, the number of people with diabetes worldwide is projected to increase from 382 million in 2013 to 592 million by 2035 [2]. Diabetic kidney disease (DKD) is one of the most important long-term complications of diabetes and the most common cause of end-stage renal disease (ESRD) worldwide. DKD occurs in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) and other secondary forms of diabetes and is defined as structural and functional renal damage manifested as clinically detected albuminuria in the presence of normal or abnormal glomerular filtration rate (GFR). It is also regarded as a characteristic microvascular complication of diabetes that is related to the duration of diabetes and involves complex interactions between environmental factors and genetic determinants.

Acute vascular rejection (AVR) is characterized by intimal arteritis in addition to tubulitis and interstitial inflammation. It is associated with a poorer prognosis compared to tubulointerstitial rejection (AIR) and AVR is associated with a higher rate of graft loss than AIR. The prognosis and treatment of arteritis without tubulitis and interstitial inflammation (isolated v1 lesion) are still controversial. We report a case of a patient who had a biopsy of the kidney allograft for evaluation of slow graft function. The biopsy revealed an isolated v1 lesion. However, we chose not to augment immunosuppression. The patient’s kidney allograft function improved over time with close monitoring. Repeat biopsy a year later showed no evidence of endothelialitis and relatively unchanged fibrosis and no other abnormalities. Although it is suggested that most cases of isolated v1 lesions will respond to corticosteroids or T cell depleting therapies, some cases will improve with conservative management. Further studies are needed to determine which cases could be managed conservatively.

Background Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in the management of cardiopulmonary failure. Continuous renal replacement therapy (CRRT) is often added to the treatment for the correction of fluid and electrolyte imbalance in patients with acute kidney injury. Most of the literature on the use of combined ECMO and CRRT has been on pediatric patients. There are limited outcome data on the use of these combined modalities in adult patients. Methods This is a retrospective analysis of all the patients above the age of 18 years who underwent combined ECMO and CRRT at a tertiary care medical center during the period January 2007 to January 2012. The primary outcomes measured were mortality at one year and renal recovery or dialysis dependence at one month. Results A total of 40 patients who were treated concurrently with ECMO and CRRT were identified. The mean age was 47.01 ± 18.29 years. The most common indications for initiation of CRRT were combined fluid overload and electrolyte imbalance. Mortality at one month was (32/40) 80%. Among the 8 survivors (20%), 3 patients required continuation of hemodialysis and 5 patients were independent of dialysis at 30 days. Conclusions Mortality of patients treated with combined ECMO and CRRT is high. Initiation of CRRT in these patients is simply an indicator of severity of illness and fatality. Younger age, higher arterial pH, left ventricular dysfunction and use of VA ECMO are associated with improved survival in these patients.

Patient: Female, 32 Final Diagnosis: Nephrogenic diabetes inspidus secondary to tubulointerstitial nephritis and uveitis (TINU) syndrome Symptoms: — Medication: — Clinical Procedure: Kidney biopsy Specialty: Nephrology Objective: Rare disease Background: Tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) is a diagnosis of exclusion based on the presence of uveitis and acute tubulointerstitial nephritis in the absence of other disease entities known to cause both of these disorders. The proximal tubule is frequently affected by this syndrome, resulting in a wide range of presentations that vary from proteinuria to full picture of Fanconi syndrome. However, distal tubular involvement is not common. Case Report: A 32-year-old female patient presented with polyuria, polydipsia and painful red eyes. Her water deprivation test and desmopressin test results were consistent with nephrogenic diabetes insipidus. Her kidney biopsy showed acute tubulointerstitial nephritis. Her eye exam was consistent with uveitis. To our knowledge, this is the first reported case of nephrogenic diabetes insipidus due to tubulointerstitial nephritis and uveitis syndrome. Conclusions: Tubulointerstitial nephritis and uveitis syndrome (TINU) syndrome can present with multiple renal tubular defects, including nephrogenic diabetes insipidus.

Infective endocarditis is a potentially life threatening condition. It is associated with high mortality and morbidity resulting mostly due to cardiorespiratory failure. Extracorporeal membrane oxygenation is a modality of treatment used to support hypoxic respiratory failure especially in patients who are already on mechanical ventilation. Continuous renal replacement therapy is added mainly for maintaining fluid and electrolyte balance. Here we report a case series of patients diagnosed with infective endocarditis who were treated with combined extracorporeal membrane oxygenation and continuous renal replacement therapy. Three patients in the age group 20-60 years were admitted with clinical features suggestive of infective endocarditis. During the course of hospital stay they developed cardiorespiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation support for refractory hypoxia. It was complicated by heart failure, renal failure and fluid overload which required initiation of continuous renal replacement therapy. All the three patients succumbed in spite of the aggressive treatment. In addition to the role played by each complication, delayed start of continuous renal replacement therapy might have also contributed to the high mortality. Early initiation of continuous renal replacement therapy for management of fluid overload needs to be considered in the management of these critically ill patients.

Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder. We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism. A diagnosis of Hashimoto’s thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy. The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto’s thyrodiitis. Induction treatment with oral cyclophosphamide and prednisone was started. At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto’s thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment.

Cryoglobulinemia is a systemic inflammatory syndrome that generally involves small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes. The therapeutic management of idiopathic cryoglobulinemic vasculitis has yet to be defined because no study has evaluated the best strategies. However, treatment of severe vasculitis is traditionally based on a combination of corticosteroids and immunosuppressants or plasmapheresis, and more recently rituximab. We report a case of 77-year-old female patient diagnosed with idiopathic cryoglobulinemia, treated successfully with 6 months prednisone tapering and 2 doses of rituximab (1 g each dose). After receiving the above-mentioned treatment, her creatinine went back to normal with resolution of proteinuria and hematuria, normalization of serum complements, and significant improvement in her clinical picture. We conclude that rituximab could be an effective treatment for idiopathic cryoglobulnemia.

Drug-induced interstitial nephritis is a recognized cause of acute and chronic renal failure. Some of them lead to the formation of granulomata. T-cell-mediated immune response is implicated in the pathogenesis. Here, we describe the case of a 74-year-old male patient with metastatic melanoma who was referred to our clinic with a history of rash and worsening renal function. Because of subacute onset, progressively worsening renal function in the presence of skin rash, elevated liver enzymes, and in the background of exposure, medication-induced interstitial nephritis was suspected. He received 3 doses of ipilimumab, a novel drug used in the treatment of metastatic melanoma within 3 months before the onset of renal failure. A renal biopsy was done, which showed granulomatous interstitial nephritis. Renal biopsy findings, temporal relation between renal failure and exposure to medication, and review of the literature supported a diagnosis of ipilimumab-induced renal failure. He was started on steroids, and renal function recovered in the next 1 month. Immune-related adverse reaction is one of the common side effects of ipilimumab. Ipilimumab-induced hepatitis and colitis has been previously reported in the literature. This is the first ever case report of ipilimumab-induced granulomatous interstitial nephritis.

Glomerulonephritis stands third in terms of the etiologies for end-stage kidney disease in the USA. The aim of this study was to look at the patterns of biopsy-proven glomerulonephritis based on data from a single center. Kidney biopsy specimens of all patients above the age of 18 years, over a 10-year period, who had diagnosis of nondiabetic glomerular disease, were selected for the study. The most common histopathological diagnosis was focal and segmental glomerulosclerosis (FSGS) (22.25%, 158/710) followed by membranous nephropathy (20.28%, 144/710) and immunoglobulin (Ig)A nephropathy (19.71%, 140/710). There was male preponderance in all histological variants except IgA nephropathy, lupus nephritis, and pauci-immune glomerulonephritis. The race distribution was uneven, and all histological variants, except minimal change disease and lupus nephritis, were more commonly seen in whites. In a separate analysis of the histological pattern in Hispanics, lupus nephritis was the most common pathology (28.70%, 62/216) followed by FSGS (18.05%, 39/216). In American Indian population, the most common pathology was IgA nephropathy (33.33%, 8/24) followed by FSGS (16.67%, 4/24). This study highlights the histopathological patterns of glomerular disease in southern Arizona. The data suggest regional and ethnic variations in glomerular disease that may point towards genetic or environmental influence in the pathogenesis of glomerular diseases.