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The Accreditation Council for Graduate Medical Education (ACGME) required that program directors receive 10-20 h/wk of protected time for program administration (including didactic teaching). In July 2022, this was reduced for all internal medicine subspecialties on the basis of program size, with 8 h/wk required for programs with fewer than seven fellows, the majority of nephrology programs.We surveyed all 151 US adult nephrology program directors (ACGME Public List of Programs 2021-2022) to determine how much protected time they receive, how much they think is necessary, and the division of their professional time. The anonymous 20-question online survey was administered from March 31 to April 30, 2022. The analysis was descriptive.Response rate was 66% (99 of 151). Geographic distribution and approved fellow positions were similar to programs nationally; 59% had fewer than seven approved positions. Median protected time was 10 h/wk (interquartile range, 5-10), with 8 h/wk (interquartile range, 5-10) for those with fewer than seven positions. Program directors estimated needing 12 h/wk (interquartile range, 10-16) to effectively administer programs, including those with fewer than seven positions, a median 5 h/wk (interquartile range, 0-7) more than received. Of program directors reporting10 h/wk for program administration, 62% provided20 hours of direct patient care. Thirty-nine percent had no protected time for core faculty. Fellow recruitment (68%) was the most time-consuming task, and didactic teaching (80%) was the most professionally rewarding.Approximately half of the nephrology programs surveyed were not in compliance with the ACGME-stipulated 10-h/wk minimum protected time for the 2021-2022 training year. Program directors estimated a median of 12 h/wk are needed to effectively manage programs.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition.METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed.RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; PCONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Interpersonal communication skills and professionalism competencies are difficult to assess among nephrology trainees. We developed a formative "Breaking Bad News" simulation and implemented a study in which nephrology fellows were assessed with regard to their skills in providing counseling to simulated patients confronting the need for kidney replacement therapy (KRT) or kidney biopsy.Observational study of communication competency in the setting of preparing for KRT for kidney failure, for KRT for acute kidney injury (AKI), or for kidney biopsy.58 first- and second-year nephrology fellows assessed during 71 clinical evaluation sessions at 8 training programs who participated in an objective structured clinical examination of simulated patients in 2017 and 2018.Fellowship training year and clinical scenario.Primary outcome was the composite score for the "overall rating" item on the Essential Elements of Communication-Global Rating Scale 2005 (EEC-GRS), as assessed by simulated patients. Secondary outcomes were the score for EEC-GRS "overall rating" item for each scenario, score 3 for any EEC-GRS item, Mini-Clinical Examination Exercise (Mini-CEX) score 3 on at least 1 item (as assessed by faculty), and faculty and fellow satisfaction with simulation exercise (via a survey they completed).Nonparametric tests of hypothesis comparing performance by fellowship year (primary goal) and scenario.Composite scores for EEC-GRS overall rating item were not significantly different between fellowship years (P = 0.2). Only 4 of 71 fellow evaluations had an unsatisfactory score for the EEC-GRS overall rating item on any scenario. On Mini-CEX, 17% scored 3 on at least 1 item in the kidney failure scenario; 37% and 53% scored 3 on at least 1 item in the AKI and kidney biopsy scenarios, respectively. In the survey, 96% of fellows and 100% of faculty reported the learning objectives were met and rated the experience good or better in 3 survey rating questions.Relatively brief time for interactions; limited familiarity with and training of simulated patients in use of EEC-GRS.The fellows scored highly on the EEC-GRS regardless of their training year, suggesting interpersonal communication competency is achieved early in training. The fellows did better with the kidney failure scenario than with the AKI and kidney biopsy scenarios. Structured simulated clinical examinations may be useful to inform curricular choices and may be a valuable assessment tool for communication and professionalism.

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group). Signal group patients were most severely affected, presenting at a mean age of 19.7 years, with the prosegment group presenting at 22.4 years, and the mature group at 37 years. Anemia was present in childhood in 91% in the signal group, 69% prosegment, and none of the mature group. REN signal peptide mutations reduced hydrophobicity of the signal peptide, which is necessary for recognition and translocation across the endoplasmic reticulum, leading to aberrant delivery of preprorenin into the cytoplasm. REN mutations in the prosegment led to deposition of prorenin and renin in the endoplasmic reticulum-Golgi intermediate compartment and decreased prorenin secretion. Mutations in mature renin led to deposition of the mutant prorenin in the endoplasmic reticulum, similar to patients with ADTKD-UMOD, with a rate of progression to end stage kidney disease (63.6 years) that was significantly slower vs. the signal (53.1 years) and prosegment groups (50.8 years) (significant hazard ratio 0.367). Thus, clinical and laboratory studies revealed subtypes of ADTKD-REN that are pathophysiologically, diagnostically, and clinically distinct.

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.

Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer.

Chronic hemodialysis is associated with significant thrombophilia. Of interest, hemodialysis patients have increased carboxyhemoglobin (COHb) and exhaled carbon monoxide (CO), signs of upregulated heme oxygenase (Hmox) activity. Given that CO enhances plasmatic coagulation, we determined whether patients requiring chronic hemodialysis had an increase in endogenous CO, plasmatic hypercoagulability and decreased fibrinolytic vulnerability. Carbon monoxide was determined by noninvasive pulse oximetry measurement of COHb. Blood samples were obtained just before hemodialysis. Thrombelastographic methods to assess plasma coagulation kinetics, fibrinolytic kinetics, and formation of carboxyhemefibrinogen (COHF) were used. Hemodialysis patients (n = 45) had abnormally increased COHb concentrations of 2.2 ± 1.9%, indicative of Hmox upregulation. Coagulation and fibrinolytic parameter normal values were determined with normal individual (n = 30) plasma. Thirty-seven patients of the hemodialysis cohort had COHF formation (82.2%, [67.9%-92.0%]; mean, [95% confidence interval]), and many of this group of patients had abnormally great velocity of clot growth (73.3%, [58.1%-85.4%]) and strength (75.6%, [60.5%-87.1%]). Furthermore, over half of COHF positive patients had a hypofibrinolytic state, evidenced by an abnormally prolonged time to maximum rate of lysis (53.3%, [37.9%-68.6%]) and clot lysis time (64.4%, [48.8%-78.1%]). Carbon monoxide enhanced coagulation and diminished fibrinolytic vulnerability in hemodialysis patients. Future investigation of hemodialysis, CO-related thrombophilia is warranted.

We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

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.

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. TMA may occur de novo or as recurrent disease post-transplant. De novo disease is usually associated with immunosuppressive drugs or can be seen as a part of endothelial damage that accompanies antibody-mediated rejection. Treatment for de novo TMA is limited to plasma exchange and change in immunosuppression. We report two cases of de novo TMA post-transplant that were successfully treated by converting to belatacept for maintenance immunosuppression.

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.

Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.

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.

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.

The role of amygdaloid nuclei in locomotion, stereotypy, and conditioned place preference (CPP) produced by psychomotor stimulants was examined. Five 2-day conditioning trials were conducted over 10 consecutive days. Rats received bilateral intracranial infusions of saline, cocaine (25-100 micrograms/side), or amphetamine (0.31-20 micrograms/side) into the ventricles (ICV), basolateral amygdala (BlA), or central amygdala (CeA) and were confined to a compartment. On alternating days, rats received sham infusions and were confined to a different compartment. Locomotion was measured daily, stereotypy was measured on trials 1 and 5, and CPP was measured 24 h after conditioning. ICV infusions of cocaine or amphetamine produced locomotion, rearing, and CPP. Intra-BlA and intra-CeA infusions of the highest dose of cocaine produced locomotion. In contrast, intra-CeA infusions of amphetamine potently produced locomotion and CPP. Intra-BlA infusions of amphetamine, however, did not produce any behavioral changes. These results suggest that the CeA, but not the BlA, is involved in initiating reward and locomotion produced by amphetamine.

The present study examined whether reserpine-induced oral dyskinesia is mediated by release of residual endogenous dopamine. Amphetamine produced a dose-dependent change in reserpine-induced oral dyskinesia in which the response was exacerbated by 0.6 mg/kg amphetamine and inhibited by 1 mg/kg. The latter dose also produced stereotypy that may have interfered with expression of reserpine-induced oral dyskinesia. Nigrostriatal 6-hydroxydopamine lesions attenuated expression of reserpine-induced oral dyskinesia. These lesions did not reduce locomotor activity, however, indicating that the attenuation of reserpine-induced oral dyskinesia was not due to a general depressant effect of the lesions on motor behavior. These results suggest that increasing dopamine release by administration of amphetamine exacerbates reserpine-induced oral dyskinesia, whereas decreasing the amount of releasable dopamine in the striatum by 6-hydroxydopamine lesions attenuates reserpine-induced oral dyskinsia. These findings may have implications for understanding tardive dyskinesia and l -3,4-dihydroxyphenylalanine ( l -DOPA)-induced dyskinesia.

One of the most common manifestations of the development of portal hypertension in the patient with cirrhosis is the appearance of ascites. Once ascites develops, the prognosis worsens and the patient becomes susceptible to complications such as bacterial peritonitis, hepatic hydrothorax, hyponatremia, and complications of diuretic therapy. As the liver disease progresses, the ascites becomes more difficult to treat and many patients develop renal failure. Most patients can be managed by diuretics which, when used correctly, will control the ascites. Spontaneous bacterial peritonitis can be treated effectively, but portends a worse prognosis. Once the ascites becomes refractory to diuretics, liver transplantation is the best option, although use of transjugular intrahepatic portosystemic shunts will control the ascites in many patients. Lastly, the development of hepatorenal syndrome indicates the patient’s liver disease is advanced, and transplantation again is the best option. However, use of vasoconstrictors may improve renal function in some patients, helping in their management while they await a liver transplant.

Podocytopenia characterizes many forms of glomerular disease, preceding the development of glomerulosclerosis. While detachment of viable podocytes from the underlying glomerular basement membrane is an important mechanism of podocyte loss, the underlying factors involved remain unclear. Secreted protein acidic and rich in cysteine (SPARC), a matricellular protein with counteradhesive properties, is normally expressed at low levels by the podocyte but is markedly increased following podocyte injury. Accordingly, we elucidate the role of SPARC in mediating experimental crescentic glomerulonephritis by inducing passive nephrotoxic nephritis in SPARC(+/+) and SPARC(-/-) mice. By days 4, 7, and 21 following disease induction, podocyte number is better preserved, glomerulosclerosis is ameliorated, and proteinuria is reduced in SPARC(-/-) mice as compared with SPARC(+/+) littermates. Moreover, the preserved podocyte number in SPARC(-/-) mice correlates with reduced urinary levels of both nephrin and podocin. To establish a causal role for SPARC in mediating detachment, cultured SPARC(+/+) and SPARC(-/-) podocytes were subjected to mechanical strain as well as trypsin digestion, and detachment assays were performed. While podocytes lacking SPARC were more resistant to stretch-induced detachment, stable re-expression of SPARC restored detachment rates to levels comparable with SPARC(+/+) podocytes. Taken together, this study proves that SPARC plays a causal role in mediating podocyte detachment and accelerating glomerulosclerosis in experimental crescentic glomerulonephritis.

Chronic reserpine administration produces persistent oral dyskinesia accompanied by severe dopamine depletion in the caudate-putamen. The present study examined whether these behavioral and neurochemical effects would persist following acute reserpine administration. Acute administration of reserpine (1 mg/kg, s.c.) produced spontaneous oral dyskinesia that persisted above control levels for at least 84 days. Reserpine also produced a 74% depletion of dopamine in the caudate-putamen relative to vehicle treatment at 3 days post-injection, but did not significantly alter dopamine in the caudate-putamen at 84 days post-injection. The finding that reserpine-induced oral dyskinesia persisted despite repletion of dopamine in the caudate-putamen suggests that the persistent neuropathological change underlying this behavior occurs in a neural pathway other than the dopaminergic nigrostriatal pathway.