Efficacy of Corticosteroids in Infection-Related Glomerulonephritis-A Randomized Controlled Trial.

Introduction: Infection-related glomerulonephritis (IRGN) is associated with glomerular immune complex deposition along with complement activation. Steroids may attenuate glomerular injury and thereby improve renal outcomes. Methods: We randomly assigned patients who had biopsy-proven IRGN and serum creatinine greater than 1.5 mg/dl to receive corticosteroids plus supportive care (intervention arm), or supportive care alone (control arm). Patients were followed up for 6 months. The primary outcome was complete renal recovery at 6 months. Safety of steroid therapy was also assessed. Results: A total of 52 patients underwent randomization. At 6 months, 17 of 26 patients (65.4%) in the intervention arm and 14 of 26 patients (53.8%) in the control arm had complete renal recovery (odds ratio 1.6; 95% confidence interval, 0.5-4.9; P = 0.397). There was no statistically significant difference in any of the secondary outcomes. Adverse events occurred in 12 patients (46.2%) in the intervention arm and 2 patients (7.7%) in the control arm (P = 0.002). Conclusion: In this single-center trial, corticosteroids did not result in a statistically significant increase in rates of complete renal recovery at 6 months. There was a significantly increased risk of adverse events associated with the use of corticosteroids.

Clinical Profile and Outcomes of Coronavirus Disease 2019 (COVID-19) in Patients Undergoing Hemodialysis.

Introduction: Several months into the coronavirus disease 2019 (COVID-19) pandemic, there remains a paucity of data on the behavior of the disease in patients with end-stage kidney disease (ESKD) on maintenance hemodialysis (MHD). Here, we describe the clinical presentations, biochemical profile, and outcomes of 183 such patients from a large tertiary-care center in South India. Materials and Methods: This prospective, observational study, included all patients with COVID-19 and ESKD who received at least one session of hemodialysis at our center, from the start of the outbreak to July 9, 2020. Clinical features at presentation, laboratory and radiological data, and outcomes were analyzed. Results: A total of 183 patients were included in the analysis. Patients who had symptoms at presentation accounted for 49.18% of the cohort, with the most common symptoms being fever (87.1%), cough (67.7%), and breathlessness (63.4%). Factors independently associated with mortality on univariate analysis included age ≥60 years, having symptoms at presentation, neutrophil-lymphocyte ratio >6, C-reactive protein >20 mg/L, serum lactate dehydrogenase >250 IU/L, CT (computed tomography) Grades 3 and 4, and the need for respiratory support. However, on multivariate logistic regression analysis, the only factor that retained significance was an age >60 years. Conclusions: This analysis confirms the previous reports of higher COVID-19-related mortality in the dialysis population and identifies older age, higher inflammatory markers, and greater degrees of radiological lung involvement to correlate with increased mortality.

Use of Remdesivir in Patients With COVID-19 on Hemodialysis: A Study of Safety and Tolerance.

BACKGROUND: There are scarce data regarding the use of remdesivir in patients with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and end-stage renal disease as US Food and Drug Administration cautions against its use in patients with an estimated glomerular filtration rate <30 ml/min/1.73m2 unless the potential benefits outweigh the potential risks. We studied the compassionate use and safety profile of remdesivir in patients with end-stage renal disease and moderate to severe SARS-CoV-2 infection. METHODS: We conducted an observational prospective study in 48 dialysis-dependent patients with SARS-CoV-2 infection who received remdesivir as part of institutional treatment protocol. During the treatment period, 100 mg of remdesivir was given 4 hours before hemodialysis sessions. Liver function tests, inflammatory markers such as serum C-reactive protein, serum ferritin and lactate dehydrogenase levels, and oxygen requirement before and after remdesivir treatment were compared. RESULTS: There were no events of significant liver function test alterations with the administration of 2 to 6 doses of remdesivir. A significant decline in serum C-reactive protein level (P < 0.001) was noted. More than two thirds (68.57%) of patients showed an improvement in oxygen requirement. Early administration of remdesivir within 48 hours of hospital admission shortened the duration of hospitalization by a mean of 5.5 days (P = 0.001). CONCLUSION: Remdesivir was well tolerated and found safe in our study. If initiated within 48 hours of hospitalization, it reduces recovery time. Assessing the mortality benefits of remdesivir in these patients requires a randomized controlled trial with a larger population.

Hansen's disease with lepra reaction presenting with IgA dominant infection related glomerulonephritis.

Various renal abnormalities in leprosy have been described largely in literature but the occurrence of IgA dominant infection related glomerulonephritis in leprosy with type 2 lepra reaction has not been reported so far. We present here a 60-year-old man with a history of leprosy in the past admitted with type 2 lepra reaction, rapidly progressive glomerulonephritis with severe renal failure requiring dialysis and diagnosed to have IgA dominant infection related glomerulonephritis.

A study of prevalence and correlates of nonadherence to immunosuppressive medications in renal transplant recipients of South Indian population and their impact on long-term graft function.

Nonadherence to immunosuppressant medications leading onto poor graft outcome is frequent among renal transplant recipients. In this study, we sought to assess the prevalence and correlates of nonadherence to immunosuppressants and its impact on graft function. A singlecenter, retrospective cum cross-sectional study of renal transplant recipients of age >18 years and who had completed at least six months after transplantation was performed. Nonadherence was assessed based on the Immunosuppressant Therapy Adherence Scale questionnaire. Factors attributed to nonadherence were assessed based on the Immunosuppressant Therapy Barriers Scale (ITBS) questionnaire. Social, economic, demographic data, and all transplant related information were recorded. Two hundred and seventy-nine patients were included in the study, of whom 78% were male. Median follow-up period was 46 months (interquartile range - 24 months to 82 months). Seventy-four patients (26.5%) admitted nonadherence to immunosuppressants. The nonadherence was significantly related to the male gender, late acute rejection episodes, rise in serum creatinine from > 0.5 mg/dL from nadir level, lower blood levels of calcineurin inhibitor, and higher ITBS scores. Refill rates and use of alarm reminders were not significantly associated with better adherence.

Crescentic infection related glomerulonephritis in adult and its outcome.

The epidemiology of infection-related glomerulonephritis (IRGN) is changing in recent times both in developed and developing nations. Although published studies showed renal outcome in adult IRGN was not as benign as in children, literature regarding clinical profile and outcome of crescentic form of adult IRGN is scarce; hence, we aimed to study the clinical profile of crescentic IRGN. We conducted a retrospective observational study in patients with crescentic IRGN in adults at the Department of Nephrology, Madras medical college, Chennai between 2009 and 2014. A total of 47 patients were included with a mean follow-up of 9.9 ± 4.2 months. The mean age was 42 ± 13.5 years. About 19.1% of patients had diabetes. The skin was the most common site of infection (38.3%) with methicillin-resistant Staphylococcus acareas (MRSA) as the most common organism. Hypocomplementemia was present in 100% in our study. Hemodialysis (HD) was required in 53.2% of patients and oral steroids were given in 78.7%. Complete renal recovery was seen only in 25.5%, progression to chronic kidney disease in 40.4%, seven patients reached end-stage renal disease, and nine patients died during follow-up. On univariate analysis, MRSA infection, the unidentified source of infection, nonisolation of organisms presence of interstitial fibrosis and tubular atrophy in renal biopsy and requirement of HD were found to be significant risk factors for poor renal outcome. In our study, crescentic form of IRGN is associated with poor renal outcome.

Clinical profile and outcome of pigment-induced nephropathy.

BACKGROUND: Pigment nephropathy represents one of the most severe complications of rhabdomyolysis or hemolysis. METHODS: We performed a retrospective observational study to analyze the etiology, clinical manifestation, laboratory profile and outcome in patients with biopsy-proven pigment-induced nephropathy between January 2011 and December 2016. History, clinical examination findings, laboratory investigations and outcome were recorded. RESULTS: A total of 46 patients were included with mean follow-up of 14 ± 5.5 months. Mean age was 40.15 ± 12.3 years, 65% were males (male:female, 1.8:1) and ∼37 (80.4%) had oliguria. Mean serum creatinine at presentation and peak creatinine were 7.5 ± 2.2 and 12.1 ± 4.3 mg/dL, respectively. Evidence of rhabdomyolysis was noted in 26 patients (64%) and hemolysis in 20 patients (36%). Etiology of rhabdomyolysis include snake envenomation (10 patients), seizures (7), strenuous exercise (5), wasp sting (2) and rifampicin induced (2). The causes of hemolysis include rifampicin induced (7 patients), sepsis (5), malaria (3), mismatched blood transfusion/transfusion reaction (3) and paroxysmal nocturnal hemoglobinuria (2). On renal biopsy, two patients had acute interstitial nephritis and two had immunoglobulin A deposits in addition to pigment nephropathy. All except one (97.8%) required hemodialysis (HD) during hospital stay and mean number of HD sessions was 9 ± 2. A total of three patients with sepsis/disseminated intravascular coagulation died, all had associated hemolysis. On statistical analysis, there was no difference between AKI due to rhabdomyolysis and hemolysis except for high creatine phosphokinase in patients with rhabdomyolysis and Lactate dehydrogenase level in patients with hemolysis. At mean follow-up, five patients (12%) progressed to chronic kidney disease (CKD). CONCLUSIONS: Pigment nephropathy due to rhabdomyolysis and hemolysis is an important cause of renal failure requiring HD. The prognosis was relatively good and depends on the etiology; however, long-term studies and follow-up are needed to assess the true incidence of CKD due to pigment nephropathy.

Unusual cause of crystalline nephropathy.

Adenine phosphoribosyltransferase deficiency is a rare, inherited autosomal recessive disease presenting with 2,8-dihydroxyadenine (DHA) urolithiasis, DHA nephropathy, and chronic kidney disease. The presence of DHA crystals in urine and renal biopsy is pathognomonic of the disease. We report a 23-year-old female with acute renal failure and nephrotic proteinuria. Urinalysis showed reddish brown, round crystals with dark outline, and central spicules consistent with 2,8-DHA crystals. Renal biopsy showed membranous nephropathy and 2,8-DHA nephropathy. Our patient improved with liberal fluid intake, restriction of high adenine content foods, and oral xanthine dehydrogenase inhibitor febuxostat. Early diagnosis and initiation of treatment prevent renal complications.

Paraneoplastic glomerulopathies associated with hematologic malignancies.

Paraneoplastic glomerulopathy (PG) includes a group of glomerular lesions that are not directly related to tumor burden, invasion, or metastasis, but induced by products from tumor cells such as hormones, growth factors, cytokines, and tumor antigens. PG was first described by Galloway in 1922, in which nephrotic syndrome (NS) secondary to Hodgkin's lymphoma was reported. They can present before, at the time of diagnosis, during remission, or at relapse of the hematological malignancies. We present three cases of paraneoplastic NS associated with hematological malignancies. Early diagnosis and treatment can alter prognosis of these patients. Paraneoplastic syndromes would remit only with proper treatment of the neoplasia.

Isolated renal involvement of cytomegalovirus inclusion disease in an infant.

Cytomegalovirus (CMV) is the most common cause of congenital infections in humans occurring in 1% of all liveborns. Symptomatic congenital CMV infection involves multiple systems and causes significant morbidity and mortality in newborns. Isolated CMV infection of the kidneys in a living infant has not been reported in literature. Here, we report an infant who presented only with renomegaly and renal biopsy showed extensive CMV inclusions. Serum and urine polymerase chain reaction for CMV were positive, and CMV involvement of other organs was ruled out. The child for treated with intravenous ganciclovir and is currently on follow-up. Cytomegalic inclusion disease involving only kidneys without other systems involvement can occur. The treatment protocol is unclear and long-term follow-up is needed.

Proliferative Glomerulonephritis with Monoclonal IgG Deposits.

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a recently described disorder that belongs to the class of monoclonal gammopathy of renal significance with the incidence of 0.17%. Monoclonal IgG deposits in glomeruli can produce a proliferative glomerulonephritis that mimics immune-complex mediated glomerulonephritis by light microscopy (LM) and electron microscopy (EM). Proper recognition of this disease requires confirmation of monoclonality by immunofluorescence (IF) staining. We present here a 50 year old female patient presented with nephrotic range proteinuria and normal renal function. Renal biopsy showed endocapillary and mesangial proliferation by LM. IF showed Ig G (+2) and C3 (+2) with positivity for Lambda light chain and Kappa light chain is negative consistent with PGNMID.

Evaluation of renal lesions and clinicopathologic correlation in rheumatoid arthritis.

The most common causes of renal disease in rheumatoid arthritis (RA) are glomerulonephritis (GN), amyloidosis, tubulo-interstitial nephritis, and drug toxicity. Our aim was to evaluate the clinicopathologic correlation of renal lesions and to assess the course and prognosis of renal disease in patients with RA. We conducted a prospective observational study in all adult patients with RA between July 2010 and June 2015. The total number of patients studied was 90, with a female:male ratio of 2.3:1. Mean follow-up duration was 30 ± 6.5 months. About 54 patients (60%) were asymptomatic. The most common symptom was edema legs (30%), followed by oliguria (10%). About 18 patients (20%) presented with the nephrotic syndrome, 15 patients (16.6%) with nephritic syndrome, and 30 (33%) with asymptomatic urinary abnormalities. Chronic kidney disease (CKD) was seen in 48 of 90 patients (53%).The most common renal pathology noted was mesangioproliferative GN followed by membranous nephropathy (MN). IgM with C3 deposits was the most common immunofluorescence pattern observed. Among the patients who had glomerular diseases, complete remission was seen in nine patients, partial remission in 15, and persistent proteinuria in 14. Duration of RA and a high erythrocyte sedimentation rate correlated significantly with persistent proteinuria. Only one patient in the glomerular disease group progressed to dialysis-dependent renal failure. On followup, 11 out of 48 CKD patients showed a significant decrease in estimated glomerular filtration rate and worsened to the next stage of CKD. Renal disease in RA presents with varied renal pathology. MN was seen frequently and was not associated with gold or penicillamine usage. Relatively high incidence of CKD was noted. Hence, it is important to monitor renal function abnormalities periodically in these patients.

Impact of acute kidney injury on renal allograft survival.

BACKGROUND: Acute kidney injury (AKI) is one of the major determinants of graft survival in kidney transplantation (KTx). Renal Transplant recipients are more vulnerable to develop AKI than general population. AKI in the transplant recipient differs from community acquired, in terms of risk factors, etiology and outcome. Our aim was to study the incidence, risk factors, etiology, outcome and the impact of AKI on graft survival. METHODS: A retrospective analysis of 219 renal transplant recipients (both live and deceased donor) was done. RESULTS: AKI was observed in 112 (51.14%) recipients, with mean age of 41.5 ± 11.2 years during follow-up of 43.2 ± 12.5 months. Etiologies of AKI were infection (47.32%), rejection (26.78%), calcineurin inhibitor (CNI) toxicity (13.39%), and recurrence of native kidney disease (NKD) (4.46%). New Onset Diabetes After Transplant (NODAT) and deceased donor transplant were the significant risk factors for AKI. During follow-up 70.53% (p = .004) of AKI recipients progressed to chronic kidney disease (CKD) in contrast to only 11.21% (p = .342) of non AKI recipients. Risk factors for CKD were AKI within first year of transplant (HR: 7.32, 95%CI: 4.37-15.32, p = .007), multiple episodes of AKI (HR: 6.92, 95%CI: 3.92-9.63, p = .008), infection (HR: 3.62, 95%CI: 2.8-5.75, p = .03) and rejection (HR: 9.92 95%CI: 5.56-12.36, p = .001). CONCLUSION: Renal transplant recipients have high risk for AKI and it hampers long-term graft survival.

Thrombotic microangiopathy as an initial manifestation in HIV patients.

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, microvascular thrombosis, and various organ dysfunctions. TMA usually occurs in a more advanced stage of HIV disease. TMA as an initial presenting feature is rare. We here report a male patient who presented with oliguric renal failure. Investigations revealed anemia, thrombocytopenia, schistocytes in peripheral smear, and HIV-positive. Renal biopsy revealed TMA. He was treated with hemodialysis and started on highly active antiretroviral therapy.

Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor.

Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far.

Wasp sting-induced acute kidney injury.

BACKGROUND: Wasp stings are a common form of envenomation in tropical countries, especially in farmers. The aim of this study was to document the clinical presentation, treatment and outcomes of patients with acute kidney injury (AKI) due to multiple wasp stings in a tertiary care hospital. METHODS: We conducted a retrospective observational study of patients with multiple wasp stings and AKI at the Department of Nephrology between July 2011 and August 2015. The clinical features, laboratory data, treatment details and outcomes were noted. RESULTS: A total of 11 patients were included. All were from rural areas. All of them were males with age ranging from 21 to 70 years, mean age 45 ± 23 years. Six had oliguria and two had hypotension. All 11 patients had evidence of rhabdomyolysis and three also had hemolysis. Ten patients required hemodialysis with a mean number of hemodialysis sessions of 8.7 ± 2.8. Renal biopsy carried out on four patients, showed acute interstitial nephritis (AIN) in one patient, acute tubular necrosis (ATN) in two patients, and one patient had both AIN and ATN. The two patients with AIN were given steroids, while all other patients were managed with supportive measures. One patient died within 48 h of presentation due to shock. At a mean follow-up of 24 months, one had progressed to chronic kidney disease and the remaining nine had normal renal function. CONCLUSIONS: Wasp sting is an occupational hazard. AKI was most commonly due to rhabdomyolysis. Early renal biopsy is indicated in those patients who do not respond to supportive measures. Timely dialysis and steroid in the case of AIN improves renal survival.

Acute kidney injury in pregnancy--a single center experience.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in pregnancy, resulting in significant maternal morbidity/mortality and fetal loss. Although the incidence of pregnancy-related acute kidney injury (PRAKI) has decreased in developed countries, it is still common in developing nations. METHODS: A prospective observational study was done between January 2010 and December 2014 to report the incidence, clinical spectrum, maternal and fetal outcome of AKI in pregnancy. RESULTS: Total number of patients: 130; mean age: 25.4 ± 4.73 years. The incidence of AKI in pregnancy was 7.8%. Most of the AKI was noted in postpartum period (68%). Etiology of AKI was sepsis (39%), pre-eclampsia (21%), placental abruption (10%), acute diarrheal disease complicating pregnancy (10%), thrombotic microangiopathy (TMA) (9%), postpartum hemorrhage (2%) and glomerular diseases (9%). Renal biopsy (n = 46) done in these patients showed renal cortical necrosis (16), TMA (11), acute tubular injury (9), acute tubulointerstitial disease (1) and glomerular disease (9). Live births occurred in 42% of patients with vaginal delivery in 34% cases. Thirty-four patients were managed conservatively, while 96 required dialysis. Complete recovery occurred in 56% and about 36% had persistent renal failure at 3 months. Mortality rate observed was 8%. In univariate analysis, low mean platelet count, higher peak serum creatinine, dialysis dependency at presentation and histopathologically presence of cortical necrosis and TMA predicted the progression to chronic kidney disease. CONCLUSION: AKI in pregnancy was common in postpartum period and sepsis being the commonest cause.