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 Uncommon Complication of a Common Tropical Infection in a Kidney Transplant Recipient - A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition due to extensive and uncontrolled immune activation. There is sparse literature on HLH in kidney transplant recipients. We report a case of a 27-year -old male kidney transplant recipient who presented with dengue fever and acute allograft dysfunction. Following improvement in allograft function with supportive treatment, he was found to have worsening pancytopenia with unusually high serum ferritin levels. Bone marrow aspiration performed for pancytopenia revealed hemophagocytosis. A diagnosis of HLH secondary to dengue viral infection was made based on the modified HLH diagnostic criteria (2009). He received supportive treatment and steroids and was discharged in a stable condition with normal kidney allograft functions. To our knowledge, this is the first case report of HLH secondary to dengue viral infection in a kidney allograft recipient managed successfully with timely diagnosis and appropriate treatment.

C3 Dominant Collapsing Focal Segmental Glomerulosclerosis - A Report of Two Rare Cases.

Collapsing focal segmental glomerulosclerosis (FSGS) a heterogeneous group of disorders, rather than a single disease entity. Kidney biopsy shows segmental or globally collapsed, sclerotic glomerular capillaries. There is also hypertrophy and hyperplasia of overlying glomerular epithelial cells. Immuno-fluorescence is negative or has non-specific deposits of immunoglobulins and C3. We present two cases of C3 dominant collapsing FSGS. Both the cases were non-responsive to therapy and had a poor outcome. This calls for research to study the role of the complement pathway in the pathogenesis of FSGS.

Gender disparity in maintenance hemodialysis units in South India: a cross-sectional observational study.

Background: Diseases manifest differently according to gender in many medical specialties. However, sex differences in kidney diseases have not been well explored worldwide, especially in India. These differences could also be attributed to sociocultural factors. Although CKD is more prevalent in women worldwide, most men are initiated on kidney replacement therapy (KRT). This study aimed to examine sex disparities in patients on maintenance hemodialysis. Materials and methods: A cross-sectional observational study was conducted in two maintenance hemodialysis units at the Institute of Nephrourology, a tertiary care referral government center in Bengaluru, India. Demographic characteristics and laboratory parameters were also recorded. Results: In total, 374 adult patients (aged >18 years) were included in the study. Most patients (72.7%) were men. Mean age in men was 46.95 ± 12.65 years, and women was 46.63 ± 13.66 years. There was no significant difference in marital status and the availability of caretakers between the groups. Spouses were the predominant caretakers for both sexes (64% men and 51% women, P = 0.14). Sons cared more for patients with mother than fathers (19.6% vs 8.8%, P = 0.074). Diabetic nephropathy was the most common cause of ESKD in both groups (33.1% vs 31.3%, P = 0.92). Men had a significantly longer duration of HTN and received more HD sessions per week than women. Mean hemoglobin (9.9 ± 1.79 vs 9.46 ± 1.47 g%) and mean serum creatinine (7.76 ± 2.65 vs 6.41 ± 2.27 mg/dl) were higher in men compared to women (P <0.002). Intradialytic complications, such as hypotension and cramps, were significantly more common in women than in men (P = 0.004). Most men (47.1%) were planning a kidney transplant (and were waitlisted) compared with fewer women (43%). There was no significant difference in the average number of hospitalizations per month or HD vintage. Conclusion: Women tend to initiate dialysis later, and a lesser number are waitlisted for kidney transplantation, which might be partly related to varying access to or delivery of health care services. Factors such as lack of education, insufficient identification of and strategies to address cultural obstacles to healthcare, and a shortage of financial means to afford medical care are potentially correctable elements that might explain this discrepancy.

Urinary exosomal miRNA signature of IgA nephropathy: a case-control study.

IgA nephropathy is the most common primary glomerulonephritis worldwide and can progress to end-stage kidney disease (ESKD). The current "gold standard" for diagnosis is kidney biopsy, which is invasive and associated with morbidity. miRNAs are small, non-coding endogenous RNA that may serve as non-invasive biomarkers, and that are found in urinary exosomes. Thus far, there is a paucity of studies of the miRNA profile for the diagnosis of IgA nephropathy. Hence, we aimed to study the urinary exosomal miRNA signature of Indian patients with IgA nephropathy. Fifty biopsy-proven IgA nephropathy patients, 50 healthy controls and 25 patients with ESKD (IgA nephropathy) were recruited over 2 years (2020-2022). Urinary exosomes were isolated from which miRNA was extracted . Analysis of urinary exosomal miRNA was done using the digital multiplexed nCounter® human v3 miRNA Expression Assay which contains 799 unique miRNA barcodes. Candidate miRNAs were identified using Lasso regression and consensus clustering. The mean age of IgA nephropathy patients was 36.32 ± 3.067 years, mean creatinine was 2.26 ± 0.318 mg/dl and mean proteinuria was 2.69 ± 0.64 g/day. Compared to healthy controls, the majority (N = 150) of miRNAs were significantly downregulated. Five candidate miRNAs (hsa.miR.146b.3p, hsa.miR.599, hsa.miR.4532, hsa.miR.664b.5p and hsa.miR.221.5p) were able to differentiate between IgA nephropathy cases and controls (AUC > 0.90); the presence of all 5 was associated with 100% specificity and sensitivity for diagnosing IgA nephropathy cases. This study of Indian patients identified that there was a significant difference in the urinary exosomal miRNA profile between IgA nephropathy cases and healthy controls, suggesting that miRNAs may be valuable in the non-invasive diagnosis of IgA nephropathy.

Changing Tides of Acute Interstitial Nephritis: A Retrospective Observational Study from South India.

Introduction: The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. Methods: A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Results: Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease. Conclusion: AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease.

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.

Wilson's Disease Presents as Recurrent Hypokalemic Muscle Paralysis.

A 21-year-old euthyroid gentleman born to nonconsanguineous parents was diagnosed with bipolar affective disorder. He presented 4 years later with hypokalemic quadriparesis. On evaluation, he was found to have features of both proximal and distal renal tubular acidosis. Ophthalmologic examination by slit lamp confirmed the presence of the Kayser-Fleischer ring. The diagnosis of Wilson's disease was established with serum ceruloplasmin levels and 24-h urinary copper levels.Here is a rare clinical presentation of Wilson's disease in the form of hypokalemic muscle paralysis due to proximal renal tubular acidosis with distal tubule involvement. The diagnosis was delayed due to the initial presentation with psychiatric symptoms.

The evolution of social media in nephrology education: A mini-review.

Social media is defined as "a group of Internet-based applications that build on the ideological and technological foundations of Web 2.0, that allow the creation and exchange of user-generated content". Social media can be used in medical education to enhance knowledge sharing among peer groups and the public in general. The internet revolutionized learning by allowing easier dissemination of knowledge that did not depend on printing and physical distribution of books, journals, or magazines. According to a report from 2018, 95% of students have access to smartphones and 45% are online at any given time. Social media platforms are powerful tools to spread knowledge by the way of stories, videos, and educational games. Both formal and informal learning can be achieved with the use of social media. The microblogging website Twitter has become a popular social media platform by many in medical education including the nephrology community. Twitter, for example, is used to build communities, discuss journal articles, inform the community of conferences, share infographics and visual abstracts of original research work. As an example, it can be difficult for women in nephrology to connect and travel to make a physical presence. The use of social media allows women to connect via webinars and Women in Nephrology (WIN) India live Twitter chats. Thus, social media can help facilitate networking and collaboration with nephrologists all over the world. Social media has limitations as well. Insensitive posts can have a detrimental effect on one's career. A survey has shown that increased use of social media can contribute to addiction, anxiety, diminished self-esteem, and even depression. Hence, in order to effectively use social media to contribute positively to one's career, we recommend considering the positive and negative aspects of social media.This review will discuss the various social media platforms and how they have been applied to nephrology education.

Urinary Ammonium in Clinical Medicine: Direct Measurement and the Urine Anion Gap as a Surrogate Marker During Metabolic Acidosis.

Ammonium is the most important component of urinary acid excretion, normally accounting for about two-third of net acid excretion. In this article, we discuss urine ammonium not only in the evaluation of metabolic acidosis but also in other clinical conditions such as chronic kidney disease. Different methods to measure urine NH4+ that have been employed over the years are discussed. The enzymatic method used by clinical laboratories in the United States to measure plasma ammonia via the glutamate dehydrogenase can be used for urine ammonium. The urine anion gap calculation can be used as a rough marker of urine ammonium in the initial bedside evaluation of metabolic acidosis such as in distal renal tubular acidosis. Urine ammonium measurements, however, should be made more available in clinical medicine for a precise evaluation of this important component of urinary acid excretion.

Targeting Glomerular Hemodynamics for Kidney Protection.

The kidney microcirculation is a unique structure as it is composed to 2 capillary beds in series: the glomerular and peritubular capillaries. The glomerular capillary bed is a high-pressure capillary bed, having a 60 mm Hg to 40 mm Hg pressure gradient, capable of producing an ultrafiltrate of plasma quantified as the glomerular filtration rate (GFR), thereby allowing for waste products to be removed and establishing sodium/volume homeostasis. Entering the glomerulus is the afferent arteriole, and the exiting one is the efferent arteriole. The concerted resistance of each of these arterioles is what is known as glomerular hemodynamics and is responsible for increasing or decreasing GFR and renal blood flow. Glomerular hemodynamics play an important role in how homeostasis is achieved. Minute-to-minute fluctuations in the GFR are achieved by constant sensing of distal delivery of sodium and chloride in the specialized cells called macula densa leading to upstream alternation in afferent arteriole resistance altering the pressure gradient for filtration. Specifically, 2 classes of medications (sodium glucose cotransporter-2 inhibitors and renin-angiotensin system blockers) have shown to be effective in long-term kidney health by altering glomerular hemodynamics. This review will discuss how tubuloglomerular feedback is achieved, and how different disease states and pharmacologic agents alter glomerular hemodynamics.

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors and CKD: Are You a #Flozinator?

Sodium/glucose cotransporter 2 (SGLT2) inhibitors have rapidly emerged as a novel therapy to reduce the rate of progression of chronic kidney disease (CKD). With humble beginnings in the 19th century for treating malaria, this class of drugs initially developed for the treatment of diabetes has now revolutionized the management of heart failure and CKD. SGLT2 inhibitors trigger glucosuria, thus modestly improving glycemic control. In addition, they have pleiotropic effects, such as reducing intraglomerular pressure and improving tubuloglomerular feedback, which lead to their beneficial effects on CKD progression. Recent data from randomized controlled trials have demonstrated the efficacy of this class of drugs in CKD. We briefly review the evidence from major trials on SGLT2 inhibitors in CKD, discuss the mechanisms of action and provide an overview of the safe and successful prescription of these medications.

Infection-related glomerulonephritis: A retrospective observational study from South India.

INTRODUCTION: Infection-related glomerulonephritis (IRGN) is an immunologically mediated renal injury due to non-renal infections. With time there has been a change with respect to its incidence, etiological agents, clinical features, and outcomes. MATERIALS AND METHODS: A retrospective observational study was conducted from May 1, 2018 to May 31, 2021. OBJECTIVES: 1. To study the clinical profile of patients with renal biopsy-proven IRGN. 2. To study the outcomes of IRGN at the end of 3 months. All patients were followed up for a minimum period of 3 months. Outcomes at the end of 3 months were categorized as any one of the following: (1) normalization of renal function tests and proteinuria < 500 mg/day, (2) persistent renal dysfunction without requirement of renal replacement therapy, (3) requirement of renal replacement therapy. RESULTS: A total of 114 patients were included in the study. The incidence of IRGN was 4.6%. The majority were males and in the fifth decade of life. Focus of infection was identified in 59.6% of cases. Acute glomerulonephritis (35.1%) and nephrotic syndrome (35.1%) were the most common syndromic presentations. 68.4% of patients had complete recovery at the end of 3 months. 15.7% of patients progressed to chronic kidney disease, and 15.7% of patients required renal replacement therapy. Elderly patients' requirement of renal replacement therapy and higher creatinine at presentation were significantly associated with poor outcomes (p < 0.05). CONCLUSION: This study emphasizes the need for early identification of the source of infection and treatment with appropriate antibiotics. Strategies to identify occult sources of infection should be employed. Elderly age and requirement of renal replacement therapy were associated with poor outcomes.

Urinary Tract Infection in Chronic Kidney Disease Population: A Clinical Observational Study.

Introduction Chronic kidney disease (CKD) is a state of chronic inflammation. Chronic inflammation weakens the body's immune response to infections. Hence, CKD patients are at an increased risk of infections. Urinary tract infection (UTI) is one of the most common types of community-acquired infection. There is a paucity of data with respect to UTI in CKD patients. Hence, our objective was to study the clinical and microbiological profile of UTI in CKD patients. Materials and methods We studied 129 CKD patients at a tertiary care hospital in south India from January 2020 to June 2020. Patients who fulfilled the inclusion criteria were included in the study. Urine samples were cultured aseptically. Only urine-culture positive samples were included in the study and antibiotic susceptibility was recorded. Results Males (76.2%) were most commonly infected. 94% were gram-negative bacteria, 3% were gram-positive bacteria and 3% were Candida species. E. coli (61.8%) was the most common isolated microorganism. Resistance to quinolones was recorded among gram-negative bacteria. Resistance to penicillin and quinolones was noted among gram-positive bacteria. Candida species were sensitive to amphotericin B and fluconazole. Conclusion The results of the study help in formulating the empiric antibiotic policy to treat UTI in CKD patients and hence prevent inadvertent use of antibiotics and the emergence of antibiotic resistance.

Coronavirus Disease 2019 and Chronic Kidney Disease - A Clinical Observational Study.

People with comorbidities are more prone to severe coronavirus disease 19 (COVID-19) infection. Chronic kidney disease (CKD) patients are commonly associated with other comorbidities such as diabetes mellitus, hypertension, or cardiovascular disease. However, there are limited data about the clinical features and laboratory parameters of COVID-19 in CKD patients. The primary objective was to study the admission clinical and laboratory parameters of COVID-19 in CKD patients. The secondary objective was to correlate the clinical and laboratory parameters at admission with mortality in CKD patients. Data were collected retrospectively from patients' medical records between July 2020 and October 2020. All CKD patients with either COVID-19 antigen or reverse transcription-polymerase chain reaction-confirmed infection were included in the study. Demographic, clinical, and laboratory data were recorded. Data of deceased and recovered patients were compared and analyzed. The mortality rate due to COVID-19 in CKD patients was 34.44%. CKD patients presented with atypical symptoms such as dyspnea (78.88%) and fatigue (73.33%) being more common than fever and sore throat. Elderly patients with comorbidities were at a higher risk of mortality (P = 0.003). CKD patients requiring renal replacement therapy (RRT) were at a higher risk of mortality than those who did not require RRT (P = 0.02). High values of high-sensitive C-reactive protein, lactate dehydrogenase, neutrophil-lymphocyte ratio, and red cell distribution width at admission were associated with a higher risk of mortality. Liver dysfunction and hypoxia at admission were also associated with a higher risk of mortality. Logistic regression analysis showed that improvements in serum albumin, serum sodium, and serum lactate were the best predictors of recovery among cases of COVID-19. In the absence of a definitive therapy or vaccine, CKD patients should be advised to follow strict social isolation practices as per the recommendations for the high-risk group of patients. These practices should be extended to dialysis units as well, which are a major hub for outbreak of infections. A meticulous triage of patients should be carried out after acquiring proper medical history because this will help to identify patients who are at an increased risk of poor outcome of the infection. Furthermore, they should be given more aggressive treatment and access to intensive care unit upon diagnosis of infection.

Subclinical Hypothyroidism (SH) and Atherogenic Index of Plasma (AIP) in Women: A Case-Control Study From a Tertiary Care Hospital in South India.

Introduction Subclinical hypothyroidism (SH) is defined as an increase in serum-thyroid stimulating hormone (S-TSH) above the normal level with free triiodothyronine (T4) and free thyroxine (T3) within the normal range. It is more common in females. The association between SH and dyslipidemia is unclear. There are many controversial studies regarding the same. This is the single largest study of Atherogenic index of plasma (AIP) in SH among women from our country. Our aim is to study the lipid profile and AIP in SH patients. We will also study the correlation between AIP and S-TSH levels in SH patients. Materials and methods It was a retrospective study conducted in a tertiary care center. A total of 97 females with SH were taken as cases and 86 normal females were taken as euthyroid (ET) controls. They were matched for demographic characteristics. T3, T4, S-TSH, total cholesterol, S-triglycerides (S-TG), high-density lipoprotein - cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and AIP were compared between the two groups. Spearman's correlation between TSH and AIP was studied in the SH group. Mann-Whitney U test was performed. Results The TG, HDL, AIP levels were significantly different between both groups. TG, AIP was higher in the SH group compared to the ET group (p value of TG= 0.01, p value of AIP <0.0001). HDL was lower in the ET group compared to the SH group (p value <0.0001). AIP showed a significant positive correlation with S-TSH levels in the SH group. (r value=0.72, p value=<0.001). Conclusion It is important to regularly monitor SH patients for dyslipidemia, in order to start early therapy with levothyroxine/statins. Emphasis should be laid on lifestyle changes such as diet and exercise from the time of diagnosis. Community level education and awareness should be encouraged. Also, AIP is a better parameter to assess cardiovascular risk in SH patients than a conventional lipid profile.

Primary hepatic neuroendocrine tumor: A rare entity.

Liver is the most common site for neuroendocrine metastasis. However, primary neuroendocrine tumor is a rare focal hepatic lesion with a better prognosis than hepatocellular carcinoma and other malignant hepatic lesions. We present a case of primary hepatic neuroendocrine tumor in a 38-year-old female patient with a radiological diagnosis of atypical focal hepatic lesion, and a confirmed diagnosis on histopathology. Few radiology features like predominant cystic component with absence of focal lesion at any other site, aids the imaging diagnosis of primary hepatic neuroendocrine tumor.