Proliferative glomerulonephritis with monoclonal IgG deposits: a unique case with a clinical course of over 46 years.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare entity first described in 2004. We present a case of PGNMID with recurrent hematuria and nephrotic range proteinuria with three biopsies over 46 years. CASE PRESENTATION: A 79-year-old Caucasian female presents with a history of two separate episodes of biopsy-proven recurrent GN over a course of 46 years. Both biopsies from 1974, and 1987 were reported as membranoproliferative GN (MPGN). The patient presented in 2016 for the third time with symptoms of fluid overload, slight worsening in renal function, and proteinuria along with glomerular hematuria. A third kidney biopsy was performed, and the final diagnosis was proliferative glomerulonephritis with monoclonal IgG/κ deposits. CONCLUSION: With three renal biopsies obtained over 46 years, our case opens a unique window into the natural history of PGNMID. The three biopsies demonstrate the immunologic and morphologic evolution of PGNMID in the kidney.

Mineralocorticoid receptor antagonists in heart failure patients with chronic kidney disease: why, when, and how?

PURPOSE OF REVIEW: Congestive heart failure (CHF) and chronic kidney disease (CKD) often coexist. However, and despite their established benefits, the use of mineralcorticoid receptor antagonists (MRAs) in patients with both comorbidities is inconsistent. This review will focus on the role of aldosterone in CHF, as well as timing, selection, and management of MRAs in CHF patients with CKD. RECENT FINDINGS: Aldosterone in CHF patients contributes to worsening sodium retention, hypokalemia, metabolic alkalosis, cardiac fibrosis, and CKD progression. MRAs are beneficial in CHF patients with CKD despite the adverse events of hyperkalemia and acute kidney injury. MRAs were previously studied in patients with CKD stage III but were recently found to be safe in end-stage kidney disease (ESKD) patients. New nonsteroidal MRAs are more selective for the mineralocorticoid receptor and have a better side effect profile. The use of potassium lowering agents, such as patriomer, helps maintain normokalemia in patients with CKD who are treated with MRAs. SUMMARY: It is recommended to use MRAs in CHF patients with normal potassium levels and a glomerular filtration rate of more than 30 ml/min. Their use is also safe in ESKD patients. In nondialysis advanced CKD patients, they may need to be combined to medications such as patiromer. New nonsteroidal MRAs are currently being studied.

Insight on the Etiologies of Chronically Elevated Troponin.

Elevated troponins signify myocardial damage and raise concern for acute coronary syndrome (ACS). However, there are medical conditions that may cause a patient to have chronically elevated troponin levels in the absence of ACS. In our extensive review, we look at the conditions and their mechanisms that cause chronically elevated troponin levels and discuss them comprehensively. We also aim for our review to serve as a guide for physicians evaluating this complex group of patients.

Inpatient hemodialysis initiation: reasons, risk factors and outcomes.

BACKGROUND/AIMS: Inpatient initiation of chronic hemodialysis is considered undesirable because of cost and possible harms of hospitalization. We examined the patient characteristics and outcomes associated with inpatient initiation. METHODS: In a prospective cohort study of incident dialysis patients, the independent association of inpatient hemodialysis initiation with patient outcomes was assessed in multivariable analyses with adjustment for patient characteristics and propensity for inpatient initiation. RESULTS: A total of 410 of 652 (63%) hemodialysis patients began as inpatients; uremia and volume overload were the most commonly documented reasons. Compared to outpatients, inpatients were more likely to be unmarried, report less social support, have multiple comorbidities and be referred to a nephrologist 4 months or less prior to initiation. Inpatient initiation was protective for subsequent all-cause hospitalization (incidence rate ratio (IRR) = 0.92, confidence interval (CI) 0.89-0.94); this was most pronounced among those who had the highest propensity for inpatient initiation (IRR = 0.66, CI 0.56-0.78), including those referred late to nephrology. Similar results were found for infectious hospitalization. Mortality [hazard ratio = 1.03, CI 0.82-1.30] and cardiovascular events were not significantly different for inpatients versus outpatients. CONCLUSION: Inpatient hemodialysis initiation has a protective association with hospitalization among those patients referred late to nephrology, with multiple comorbidities and/or little social support.

Lymphoma-Associated Monoclonal Cryoglobulinemic Glomerulonephritis and Relationship with Hepatitis C Virus Infection: A Case Report.

We report a case of type I cryoglobulinemic glomerulonephritis in a patient with chronic hepatitis C who presented with acute renal failure. The renal biopsy revealed membranoproliferative GN (MPGN) due to cryoglobulinemia with unexpected monoclonal Kappa restriction on immunofluorescence microscopy, suggesting an underlying hematopoietic malignancy. The bone marrow biopsy revealed presence of marginal zone lymphoma. Our case raises awareness regarding possibility of monoclonality in the renal biopsy of HCV-infected patients and exemplifies the crucial role the renal biopsy plays in detecting lymphoid malignancies where clinical features are ambiguous.

Hypertriglyceridemia and peripheral neuropathy in neurologically asymptomatic patients.

OBJECTIVES: In this study we intended to find a correlation between hypertriglyceridemia and peripheral neuropathy (PN) in patients with a high triglyceride level and no neurological complaints. METHODS: We recruited 24 patients (21 males and 3 females) having a triglyceride level above 300 mg/dl with no neurologic complaints and none of the other common causes of PN and they underwent an electroneurographic study. The distal motor or sensory latencies (DL), motor or sensory conduction velocities (CV), and motor or sensory amplitudes (AMP) were collected for the peroneal, posterior tibial, sural, median, and ulnar nerves and were considered abnormal if they fall above or below 2 standard deviations of reference values. RESULTS: Our results show that 70.8% of the patients had a significant delay in the DL of the sural nerves and 66.7% had a significant delay in the DL of the median sensory fibers. 54.2% of the patients had a significant decrease in the motor CV in the posterior tibial nerves and 33.3% had a significant decrease in the sensory CV in the sural nerves. The means of the DL and CV were significantly different from reference values in most of the nerves. Amplitudes were the least if at all affected. CONCLUSION: The pattern of the abnormalities affecting more the DL, the sensory nerves and the longer nerves of the lower extremities is suggestive of an early axonal polyneuropathy. We conclude that hypertriglyceridemia affects conduction parameters in peripheral nerves in a trend suggestive of early peripheral neuropathy.

Functional genomic analysis identifies indoxyl sulfate as a major, poorly dialyzable uremic toxin in end-stage renal disease.

BACKGROUND: Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). METHODS: We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). RESULTS: Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. CONCLUSION: These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

Tobacco use by university students, Lebanon, 2001.

AIMS: The objective was to determine the prevalence of smoking [cigarettes and/or narghile (i.e. water-pipe)] among university students and to examine multiple correlates. DESIGN: Cross-sectional. SETTING: Beirut, Lebanon. PARTICIPANTS: A proportionate random sample of 1964 students from public and private universities in Beirut, Lebanon. MEASUREMENTS: Participants completed a self-administered anonymous questionnaire that included demographic and scholastic items and health behavioral aspects, including smoking, alcohol, physical activity, weight control measures and seat belt use. FINDINGS: The overall prevalence of smoking was 40% (21.1%, 7.6% and 11.3% of the students were smoking only narghile, only cigarettes and both cigarettes and narghile, respectively). Regression analyses showed that males, those of non-Lebanese origin, pursuing undergraduate degrees, performing risky weight control measures and drinking excessive amounts of alcohol had increased odds of smoking cigarettes. Also, age, high level of paternal education and field of study were significant predictors. Narghile smoking was significantly higher among males who drank excessive alcohol. CONCLUSIONS: The authors advocate a collaborative effort to alleviate the consequences of smoking among university students.

Negative effect of leptin on bone mass in type 1 diabetes.

Studies investigating the effect of leptin on bone mass were inconsistent and some related it to the effect of insulin. We intend in this cross-sectional study to investigate the effect of leptin on bone mass in type 1 diabetic patients. We recruited 42 patients with type 1 diabetes for which we determined weight, height, HbA1c, microalbuminuria, serum leptin, bone mineral content (BMC) and density (BMD), and body composition. The patients had an average age of 20.1 +/- 0.6 years, an average body mass index (BMI) of 23.6 +/- 0.5 kg/cm(2) and an average duration of diabetes of 9.1 +/- 1.0 years. The Z-score was not correlated with HbA1c or duration of the disease, and the average Z-score was not different in patients with microalbuminuria as compared to patients with no reported microalbuminuria. On the other hand, Z-score and BMC correlated negatively with leptin (r = -0.31; p = 0.04 and -0.60, p < 0.01, respectively). These correlations persisted after adjustment for fat mass. We conclude that not metabolic control of diabetes, but serum leptin has a negative effect on bone density in young patients with type 1 diabetes. This negative effect of leptin on bone density maybe, in part, due to deficiency of endogenous insulin secretion in these patients.