Multiple Facets of Multiple Myeloma in Kidney Biopsy: A Multicenter Retrospective Study.

Introduction: Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. Objective: To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. Materials and Methods: A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. Results: A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Conclusion: Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis.

An Updated Review of Membranous Nephropathy.

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor (PLA2R) as a target antigen has led to a paradigm shift in the understanding and management of MN. At present, serum PLA2R antibodies are used for diagnosis, prognostication, and guiding treatment. Now, with the discovery of more than 20 novel target antigens, antigen mapping is almost complete. The clinical association of certain antigens provides clues for clinicians, such as the association of nerve epidermal growth factor-like 1 with malignancies and indigenous medicines. Serum antibodies are detected for most target antigens, except exostosin 1 and 2 and transforming growth factor-beta receptor 3, but their clinical utility is yet to be defined. Genome-wide association studies and studies investigating environmental factors, such as air pollution, shed more light on the underpinnings of MN. The standard therapy of MN diversified from cyclical cyclophosphamide and steroids to include rituximab and calcineurin inhibitors over the past decades. Here, we provide a cutting-edge review of MN, focusing on genetics, immune system and environmental factors, novel target antigens and their clinical characteristics, and currently available and emerging novel therapies in MN.

A Multicenter Retrospective Cohort Study on Management Protocols and Clinical Outcomes After ABO-incompatible Kidney Transplantation in India.

BACKGROUND: There is no robust evidence-based data for ABO-incompatible kidney transplantation (ABOiKT) from emerging countries. METHODS: Data from 1759 living donor ABOiKT and 33 157 ABO-compatible kidney transplantations (ABOcKT) performed in India between March 5, 2011, and July 2, 2022, were included in this retrospective, multicenter (n = 25) study. The primary outcomes included management protocols, mortality, graft loss, and biopsy-proven acute rejection (BPAR). RESULTS: Protocol included rituximab 100 (232 [13.18%]), 200 (877 [49.85%]), and 500 mg (569 [32.34%]); immunoadsorption (IA) (145 [8.24%]), IVIG (663 [37.69%]), and no induction 200 (11.37%). Mortality, graft loss, and BPAR were reported in 167 (9.49%), 136 (7.73%), and 228 (12.96%) patients, respectively, over a median follow-up of 36.3 mo. In cox proportional hazard model, mortality was higher with IA (hazard ratio [HR]: 2.53 [1.62-3.97]; P < 0.001), BPAR (HR: 1.83 [1.25-2.69]; P = 0.0020), and graft loss (HR: 1.66 [1.05-2.64]; P = 0.0310); improved graft survival was associated with IVIG (HR: 0.44 [0.26-0.72]; P = 0.0010); higher BPAR was reported with conventional tube method (HR: 3.22 [1.9-5.46]; P < 0.0001) and IA use (HR: 2 [1.37-2.92]; P < 0.0001), whereas lower BPAR was reported in the prepandemic era (HR: 0.61 [0.43-0.88]; P = 0.008). Primary outcomes were not associated with rituximab dosing or high preconditioning/presurgery anti-A/anti-B titers. Incidence of overall infection 306 (17.39%), cytomegalovirus 66 (3.75%), and BK virus polyoma virus 20 (1.13%) was low. In unmatched univariate analysis, the outcomes between ABOiKT and ABOcKT were comparable. CONCLUSIONS: Our largest multicenter study on ABOiKT provides insights into various protocols and management strategies with results comparable to those of ABOcKT.

PARAKID: Navigating the relation between paraproteins and kidney lesions: A multi-center retrospective observational study.

INTRODUCTION: Monoclonal gammopathy is a heterogeneous group of disorders due to the clonal proliferation of immunoglobulin-producing plasma cells or B lymphocytes. Patients develop kidney disease not only due to malignant transformation but also due to the idiosyncratic properties of the M protein and the host factors. We aim to study the spectrum of kidney diseases in patients with paraproteinemia. MATERIALS AND METHODS: A retrospective observational study was performed at three tertiary care centers in Southern India. Kidney biopsies conducted in these three centers were reviewed from June 1, 2020 to November 30, 2022. All biopsies suggestive of monotypic immunoglobulin or light chain restriction were included in the study. RESULTS: A total of 122 patients were included in the study with an incidence of 2.4%. The mean age was 52.27 ± 13.27 years, and majority (63.1%) were males. AL amyloidosis was most common in the monoclonal gammopathy of renal significance (MGRS) group, and cast nephropathy was most common in the multiple myeloma (MM) group. On histopathology, 83.6% had a single lesion, followed by 14.8% with double lesion, and 1.6% with triple lesion. CONCLUSION: Paraproteinemia is associated with a myriad of kidney lesions. MGRS and MM are usually present in the 6th decade of life and beyond, while proliferative glomerulonephritis with monoclonal immunoglobulin deposits is more common in the younger age group. Older age group, high creatinine, hyperuricemia, hyperphosphatemia, presence of more than one lesion on kidney biopsy, and presence of cast nephropathy was significantly associated with the requirement of kidney replacement therapy.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

Kidney transplant dysfunction in a patient with COVID - 19 infection: role of concurrent Sars-Cov 2 nephropathy, chronic rejection and vitamin C-mediated hyperoxalosis: case report.

BACKGROUND: COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure. CASE PRESENTATION: A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India. CONCLUSIONS: This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India.

BACKGROUND: There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS: Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS: COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS: Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.

Nondiabetic Renal Pathology in Biopsies of Type 2 Diabetes Mellitus Patients: Changing Trends and the Clinical Factors Predicting These Lesions.

The underlying histopathology of diabetic kidney disease is classically described as diabetic glomerulosclerosis (DGS). Over the years, it has been noted that kidney biopsies in type 2 diabetes mellitus (T2DM) patients are revealing lesions other than DGS because of the changing natural history of diabetic kidney disease. A retrospective study of all kidney biopsies in T2DM patients over a three-year period submitted to the Pathology Departments of Apollo Hospitals, Hyderabad, and Yashoda Hospitals, Secunderabad, India, was analyzed. The clinical data were analyzed for the type of biopsy lesions and the clinical predictors of nondiabetic renal pathology in these biopsies. The result of this study was compared with another study published by one of the authors in 2006. A total of 1029 biopsies were obtained from the records. Pure DGS was seen in 341 (33.1%) and nondiabetic renal lesions were seen in 482 (46.8%) biopsies. The most common histological lesion in the isolated nondiabetic renal disease group was interstitial nephritis (acute and chronic). Incidence of minimal change disease and membranous nephropathy is significantly less in the current cohort. The factors which were predictive of isolated nondiabetic lesions were short duration of diabetes and renal failure (unexplained/rapid deterioration). 66.9% of biopsies show nondiabetic-renal lesion histopathology in T2DM patients. This offers the clinician an opportunity to consider specific treatment wherever possible.

Unusual cause of irreversible acute kidney injury postgastrectomy.

A 56-year-old male was diagnosed to have carcinoma stomach following evaluation of lack of appetite and weight loss. He underwent neoadjuvant chemotherapy and gastrectomy. Following surgery he developed progressive renal failure. A renal biopsy led to the diagnosis of oxalate nephropathy. Despite treatment his renal functions never recovered. Oxalate nephropathy is an underappreciated cause of renal failure postgastrectomy. It can cause irreversible renal failure unless detected and treated early.

Acute Interstitial Nephritis in a Patient with High Aluminum Blood Levels: A Case Report.

A known case of hypertension and recent onset diabetes presented to our neurological clinic with symptoms of ataxia, rigidity, and tremors. His symptoms were of relatively recent onset. He gave no history of any renal disease in past. The magnetic resonance imaging of the brain done by the neurologist was suggestive of demyelinating pathology. His renal functions showed progressive deterioration (Cr 1.4 mg/dl about 3 months back to 2.2 mg/dl at present) along with the onset of his neurological illness. An extensive work up for autoimmune encephalitis and paraneoplastic syndrome was noncontributory. A toxicology screen revealed high levels of aluminum in the blood. A renal biopsy showed features of interstitial nephritis and predominant vacuolar injury of the proximal tubule (suggestive of toxic injury.) On further questioning, the patient gave history of using an over the counter native medication. The medication was stopped and weekly desferrioxime chelation advised. A short course of steroids (0.5 mg/kg/day tapering dose for 6 weeks) was also given. The creatinine stabilized to 1.3 mg/dl on follow-up after 3 months. The neurological symptoms also resolved completely.

Coexistent Amyloid Fibrils in a Patient with Combined Light Chain Deposition Disease and Light Chain Cast Nephropathy.

Monoclonal secretion of light chains can affect the kidney with varied morphologic manifestations. Myeloma cast nephropathy, proximal tubulopathies, monoclonal immunoglobulin deposition disease, amyloidosis, and tubulointerstitial nephritis are often noted in the renal biopsy of these patients. Most often the histopathological manifestations affect only one compartment of the nephron (tubules, capillaries, glomerulus). Case reports of a combination of cast nephropathy and monoclonal light chain deposition disease are also reported in literature. Here we report an unusual case of coexisting cast nephropathy, light chain deposition disease, and deposition of amyloid fibrils in the biopsy of a lady with monoclonal kappa light chain excretion.

Mammalian target of rapamycin inhibitors in a patient with polycystic kidney disease-1-tuberous sclerosis-2 contiguous gene syndrome.

The mutations associated with polycystic kidney disease are closely aligned with that of tuberous sclerosis (TSC) in chromosome 16. Occasionally, the presence of these mutations in an individual can lead to a presence of a disease phenotype with a combination of polycystic kidney disease and TSC (contiguous gene syndrome). We present a case report of a young girl who presented with skin lesions, central nervous system tubers, and cystic disease of the kidneys. She was treated with mammalian target of rapamycin inhibitors with a favorable outcome.

Immunoglobin G4-related disease: Two case reports and review of the recent literature.

IgG4-related disease (IgG4-RD) is a new, multiorgan and constantly evolving disease characterized by IgG4-positive plasma cells in the affected organ. This disease often affects the elderly. The pancreas is the main target organ affected, with almost all organs in the body being affected. A large amount of studies have been conducted to understand the pathogenesis of the disease and its spectrum. For accurate diagnosis of the condition, an adequate knowledge of imaging findings, clinical presentations and laboratory reports is essential. We report two cases of the IgG4-RD and review the recent literature about this increasingly recognized entity.

Primary cutaneous cryptococcosis due to Cryptococcous laurentii in a renal transplant recipient.

We report a patient with primary cutaneous cryptococcosis caused by Cryptococcous laurentii following renal transplantation, probably due to repeated insulin and heparin subcutaneous injections on his thigh. Although cutaneous cryptococcosis due to C. neoformans is well known, reports of skin infections due to non-neoformans cryptococci are uncommon.

Renal failure in a patient with primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APLA) is a syndrome complex characterized by recurrent arterial or venous thrombosis, recurrent fetal wastage, thrombocytopenia and presence in serum of antibodies against negatively charged phospholipids like lupus anticoagulant (LA), anticardiolipin antibody (ACLA) and subgroups. These are classified further as primary (wherein this occurs in isolation) and secondary (associated with infection, drugs and malignancies). It is uncommon to find both LA and ACLA in primary APLA syndrome (unlike as in the secondary form). Renal manifestations which include renal arterial and venous occlusion and infarction and thrombotic microangiopathy have also been infrequently described. We hereby present a case of primary APLA syndrome with unusual features of LA and ACLA occurring together and also the presence of renal failure due to left renal artery thrombosis and right renal artery occlusion.