Histological Spectrum of Clinical Kidney Disease in Type 2 Diabetes Mellitus Patients with special Reference to nonalbuminuric Diabetic Nephropathy: A Kidney Biopsy-based Study.

BACKGROUND: Diabetic nephropathy (DN) is an important and catastrophic complication of diabetes mellitus (DM). Kidney disease has heterogeneity in histology in diabetes patients and includes both diabetic kidney disease (DKD) (albuminuric or nonalbuminuric) and nondiabetic kidney disease (NDKD) either in isolation or in coexistence with DN. Diabetic nephropathy is hard to overturn. While NDKD is treatable and reversible. MATERIALS AND METHODS: We enrolled a total of 50 type 2 diabetes mellitus (T2DM) patients with clinical kidney disease, of both genders and age >18 years, who underwent kidney biopsy from October 2016 to October 2018. Patients with proteinuria <30 mg per day were excluded from the study. The indications of the renal biopsy were nephrotic syndrome (NS), active urinary sediment, rapid decline in renal function, asymptomatic proteinuria, and hematuria. RESULT: A total of 50 (males: 42 and females: eight) patients with T2DM who underwent kidney biopsy were enrolled. The clinical presentation was: NS 26 (52%), chronic kidney disease (CKD) 11 (22%), asymptomatic proteinuria and hematuria six (12%), acute kidney injury (AKI) four (8%), and acute nephritic syndrome (ANS) three (6%). Diabetic retinopathy (DR) was noted in 19 (38%) cases. Kidney biopsy revealed isolated DN, isolated NDKD, and NDKD superimposed on DN in 26 (52%), 14 (28%), and 10 (20%) cases, respectively. Idiopathic membranous nephropathy (MN) (4) and amyloidosis (2) were the most common forms of NDKD, whereas diffuse proliferative glomerulonephritis (DPGN) was the main form of NDKD superimposed on DN. Diabetic nephropathy was observed in 15 (79%) cases in presence of DR and also in 11 (35.5%) cases even in absence of DR. Of eight patients with microalbuminuria four (50%) cases have biopsy-proven DN. CONCLUSION: About 48% of patients had NDKD either in isolation or in coexistence with DN. Diabetic nephropathy was found in absence of DR and in patients with a low level of proteinuria. The level of proteinuria and presence of DR does not help to distinguish DN vs NDKD. Hence, renal biopsy may be useful in selected T2DM patients with clinical kidney disease to diagnose NDKD.

Outcome of HIV Related Kidney Diseases Treated with Combined Antiretroviral Therapy (cART).

INTRODUCTION: The safe and effective treatment of HIV-associated renal diseases with cART can decrease the progression to ESRD and also improve the morbidity and mortality secondary to renal failure. MATERIAL AND METHODS: HIV positive patients with clinical kidney disease were the subjects of this study. The diagnosis of HIV was established using immunochromatographic assays. The patients were subjected to meticulous history, physical examination, laboratory investigations and kidney biopsy. Patients were treated with combined antiretroviral therapy and enalapril. They were followed at 3 months interval for one year. Short term outcome was assessed using changes in serum creatinine and proteinuria. Long term outcome assessments were done using progression to end stage renal disease and patients survival. RESULT: Ten (Male=7; Female=3) HIV patients with clinical renal disease were included in this study. Their age ranged between 26-55 (Mean=40.5±8.8) years. The mean serum creatinine at the baseline, three, six, nine and twelve months was 2.46, 2.09, 2.43, 2.46 and 2.58 mg/dl respectively. The mean e-GFR by MDRD equation at 0, 3, 6, 9 and 12 months was 40.9, 45.5, 48.2, 51.1 and 52.5 ml/ min/1.73m2 respectively. The mean twenty four hour urinary protein excretion at 0, 3, 6, 9 and 12 months was 3.01, 2.82, 2.22, 2.02 and 1.79 grams respectively. Six patients showed improvement in creatinine and e-GFR, whereas worsening of renal function was seen in four patients. Proteinuria decreased in seven patients, whereas it remained unchanged in three patients. There was no mortality at the end of one year of follow up. CONCLUSION: Treatment with combined ART and ACEIs slows the progression of HIV-associated kidney disease, decreases proteinuria and improves the GFR.

Etiopathological Study of Crescentic Glomerulonephritis and its Outcome: A Retrospective Analysis.

INTRODUCTION: Crescentic Glomerulonephritis (CGN) is most aggressive structural phenotype and accounts for 2%-7% of renal biopsy in most series. The aim of study was to assess the clinical feature and outcome of CGN at our centre. MATERIAL AND METHODS: The renal biopsy performed during the period of January 2015 to January 2018 was studied and patients showing crescentic glomerulonephritis on histology were selected for this study. The clinical presentation, immunological assay, biochemical and haematological investigations, treatment protocol and final outcome at three month of these patients were analysed in the present study. RESULTS: Of 380 biopsy, 26 (male=17, female=9) patients had histological evidence of CGN (6.8%). The age of patients ranged between 13-75 (mean=43) years. Fibro cellular and cellular crescent was noted in 84.61% and 15.38% of patients respectively. Small vessels vasculitis and granuloma was observed in 5 (19.23%) cases. Based on immunohistopathology, we observed type I (n=3), type II (n=8), type III (n=5), type IV (n=3), and type V (n=7) crescentic GN in 11.53%, 30.76%, 19.23%, 11.53% and 26.92% of patients respectively. Haemodialysis was given to 22(84.61%) and 4(15.38%) patients were treated with immunosuppressive therapy. Plasmapheresis was used in two double positive (ANCA + Anti GBM Ab) patients. Remaining 21(80.76%) has progressed to ESRD over a period of 2-3 months. CONCLUSION: Type II (immune complex) CGN was most common type followed by type V (immune negative) and type III (pauci-immune) CGN. The crescentic GN had worse prognosis with >80% of patients progressed to ESRD within 3 month of time from onset of illness. Early diagnosis and treatment is associated with favourable outcome.

Heterogeneity in Kidney Histology and Its Clinical Indicators in Type 2 Diabetes Mellitus: A Retrospective Study.

The heterogeneous spectrum of kidney disease in diabetes ranges from albuminuric or non-albuminuric diabetic kidney disease to non-diabetic kidney diseases. Presumptive clinical diagnosis of diabetic kidney disease may lead to an erroneous diagnosis. MATERIAL AND METHOD: We analyzed the clinical profile and kidney biopsy of a total of 66 type 2 diabetes patients. Based on kidney histology, they were divided into-Class I (Diabetic Nephropathy), Class II (Non-diabetic kidney disease), and Class III (Mixed lesion). Demographic data, clinical presentation, and laboratory values were collected and analyzed. This study tried to examine the heterogeneity in kidney disease, its clinical indicator, and the role of kidney biopsy in the diagnosis of kidney disease in diabetes. RESULTS: Class I consisted of 36(54.5%), class II 17(25.8%), and class III 13(19.7%) patients. The commonest clinical presentation was nephrotic syndrome 33(50%) followed by chronic kidney disease 16(24.4%) and asymptomatic urinary abnormality 8(12.1%). Diabetic retinopathy (DR) was present in 27(41%) cases. DR was significantly higher in the class I patients (p < 0.05). Specificity and positive predictive values of DR for DN were 0.83 and 0.81, respectively (sensitivity 0.61; negative predictive values 0.64). The Association of the duration of diabetes and the level of proteinuria with DN was statistically not significant (p > 0.05). Idiopathic MN (6) and Amyloidosis (2) were the most common isolated NDKD; whereas diffuse proliferative glomerulonephritis (DPGN) (7) was the commonest NDKD in mixed disease. Another common form of NDKD in mixed disease was Thrombotic Microangiopathy (2) and IgA nephropathy (2). NDKD was observed in 5(18.5%) cases in presence of DR. We noted biopsy-proven DN even in 14(35.9%) cases without DR, in 4(50%) cases with microalbuminuria and 14(38.9%) cases with a short duration of diabetes. CONCLUSION: Almost half (45%) of cases with atypical presentation have non-diabetic kidney disease (NDKD), though even among these cases with atypical presentation diabetic nephropathy (either alone or in mixed form) is commonly seen in 74.2% of cases. DN has been seen in a subset of cases without DR, with microalbuminuria, and with a short duration of diabetes. Clinical indicators were insensitive in distinguishing DN Vs NDKD. Hence, a kidney biopsy may be a potential tool for the accurate diagnosis of kidney disease.

A Case of Dyke-Davidoff-Masson Syndrome with Hypoplasia of the Kidney: An Unusual Association.

Dyke-Davidoff-Masson syndrome (DDMS) is a rare neuro-osteal syndrome of childhood and a constellation of cerebral hemiatrophy, facial asymmetry, seizures, osseous changes, and hemiplegia. It commonly presents with seizures and hemiplegia. The involvement of the kidney in DDMS is not known in the available literature, except in a case report that described ectopic kidney in DDMS. We present the case of a 15-year-old boy who presented with recurrent seizures, right facial palsy, left hemiparesis, and advanced renal failure. The neuroimaging revealed diffuse right cerebral atrophy, dilatation of the ipsilateral lateral ventricle, and ipsilateral thickening of the calvaria. The nephrological evaluation suggested the diagnosis of chronic kidney disease stage VD, probably secondary to congenital hypoplasia of the kidney.

Outcome of COVID-19 in Kidney Transplant Patients from Eastern India: A Single Center Study.

Introduction: COVID-19 in kidney transplant recipients (KTR) had been associated with high incidence of acute kidney injury and higher mortality. Management of these patients is still evolving. Methods: A retrospective observational study was done that included all KTR aged ≥18 years and ≤65 years who had COVID-19 diagnosis via RTPCR test between 1 June 2020 and 30 May 2021. Severity of COVID-19 was determined as per the guidelines given by Government of India. Acute kidney injury was defined according to KDIGO guideline. Data was collected and analyzed using SPSS version 16.0 (Chicago, SPSS Inc.). Results: Out of 34 patients, 29 were men. Median age of patients was 39.9 years and median time since transplantation was 34 months. Presenting symptoms were fever (100%), cough (79.4%), gastrointestinal symptoms (23.5%), and dysgeusia/anosmia (23.5%). COVID-19 was severe in 17.6%, moderately severe in 32.4%, and mild in 50% of patients. Time since transplantation, duration of symptoms, hospital stay and inflammatory markers like CRP, LDH, ferritin and d-dimer were significantly associated with disease severity (P < 0.05). Steroids were increased in 55%, antiproliferative agents stopped in 97%, and calcineurin inhibitors stopped in 26% of patients. 70.6% of the patients were managed in home isolation. Acute kidney injury occurred in 58.8% cases. 75% of the AKI patients recovered by 28 days after discharge. Conclusion: Our study showed that outcome of COVID-19 in kidney transplant patients was reasonably good.

Neutralizing antibody response against subcutaneously injected bacteriophages in rabbit model.

Bacteriophage therapy is currently experiencing a renaissance. Therapeutic efficacy of bacteriophages depends on phage-bacterial and phage-host interactions. The appearance of neutralizing anti-phage antibody has been speculated to be one of the few reasons for bacteriophage therapy's failure. This study aimed to know whether there is a rise in the neutralizing antibody on the parenteral injection of bacteriophages in an animal model. This study included bacteriophages against five different bacteria, namely Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella Typhi and Staphylococcus aureus. These bacteriophages were isolated, propagated and purified. Bacteriophage specificity was confirmed by spot testing on the respective bacterial lawn. Weekly subcutaneous injection of purified bacteriophages (109PFU) was given to five rabbits for six weeks. Blood samples were collected before administering the next dose every week. The antibody response was tested by phage neutralization followed by plaque assay by using double agar overlay method. The rise in anti-phage neutralizing antibodies was observed usually after the 3rd week after immunization. Complete neutralization of bacteriophages could be seen between 3 and 5 weeks after immunization. A further rise in bacteriophage counts (PFU), especially on 1:1000 and 1:2000 serum dilutions, could be noticed by the end of 6th week against most bacteriophages injected. Background anti-phage neutralizing antibodies were observed against bacteriophage specific to Escherichia coli. However, it was absent against bacteriophages specific to other four bacteria. Bacteriophage interacts with mammalian host and induces anti-phages neutralizing antibody production. However, neutralization of phage depends on repeated administration and duration of therapy. The significant rise in neutralizing antibody could be seen at the end of 3rd week. Therefore, bacteriophage can be effectively used in acute cases where therapy duration is less than 2 weeks. However, for prolonged therapy, bacteriophage cocktail of different antigenicity may be suggested.

Thyroid function in patients with idiopathic nephrotic syndrome.

BACKGROUND: Albumin is the major protein excreted in urine in patients with nephrotic syndrome (NS). However, low-molecular-weight proteins including some binding proteins are also excreted. Thyroid hormone and its binding globulins are excreted in urine in excess in nephrotic syndrome. Therefore, it has been postulated that patients with nephrotic syndrome may show hypothyroidism, subclinical or overt. METHODS: In this prospective observational study, patients of idiopathic nephrotic syndrome aged 1-40 years of both gender were included. Serum T3, T4 and TSH were assayed at diagnosis and repeated at 12 weeks or at remission whichever was earlier. Renal biopsy was performed as required. RESULTS: Among 100 patients taken for analysis (42 children, 58 adult), 30 cases were of first episode, 40 were of frequent relapse/steroid-dependent NS, and 30 patients had steroid-resistant NS (SRNS). Three (3%) cases had overt hypothyroidism and 18 (18%) patients had subclinical hypothyroidism. Most hypothyroid cases belonged to SRNS subgroup. Mean Serum T3, T4 and TSH values showed significant improvement in remission in comparison to nephrosis state (P < 0.01). Serum TSH had significant positive correlation (r = 0.391, P < 0.01) with 24-h proteinuria and negative correlation with serum albumin (r = - 0.303, P < 0.01) in nephrosis. CONCLUSION: Hypothyroidism is common among nephrotic syndrome patients especially in SRNS subgroup. Therefore, routine screening is recommended in steroid-resistant nephrotic syndrome patients.

Outcomes of hospital-acquired acute kidney injury in elderly patients: a single-centre study.

BACKGROUND: HAAKI is a common clinical problem in hospitalized patients. Its incidence is high in older patients and carries worse prognosis. The presence of multiple co-morbidities, aging process, and frequent diagnostic and therapeutic interventions predispose elderly patients to HAAKI. This study aims to evaluate the spectrum, risk factors and determinants of outcome of elderly patients with HAAKI. METHODS: This prospective study was conducted during January 2014 to September 2015 in the Department of nephrology, Institute of Medical Sciences, BHU, Varanasi, UP, India. First 100 HAAKI elderly (> 60 years) patients, who fulfilled the inclusion criteria were enrolled for study. HAAKI was defined as per RIFLE criteria after minimum 48 h of hospitalization. Clinical, biochemical, and radiological evaluation were done. Follow up was done till discharge or up to 30 days whichever was later. RESULTS: Till selection and enrollment of first 100 HAAKI patients, total 23507 patients were hospitalized. 11.2% (n = 2635) patients were ≥ 60 years of age. Among 2635 elderly patients, 3.79% (n = 100) developed HAAKI. Commonest causes of HAAKI were sepsis (37%) followed by drugs like NSAID, Contrast agent, Amphotericin B, and antibiotics including amino glycosides in (24%) patents. DM and HTN were the commonest risk factors. Mortality was noted in 45% cases and rest 55% patients recovered with partial or full recovery of renal function. ICU admission, Oliguria, RIFLE-F, need of RRT, and SOFA score > 11 were independent determinants of outcome of elderly patients with HAAKI. CONCLUSION: HAAKI is associated with increased morbidity and mortality in elderly patients. Associated co-morbid conditions predispose elderly patients to HAAKI. ICU admission, Oliguria, severity of renal failure, requirement of RRT, and initial SOFA score were strong predictors of survival of elderly patients with HAAKI.