Acute Kidney Injury in a Tertiary Care Center of South India.

Background and Objective: Data regarding the epidemiology and outcomes of acute kidney injury (AKI) from our part of the world are limited. The irking consequences of AKI, both on the patient and the health care system, are being increasingly recognized. We aimed to study the epidemiology and short-term outcomes of AKI and to analyze the factors associated with adverse renal outcomes. Materials and Methods: We retrospectively studied AKI patients stratified according to the Kidney Disease: Improving Global Outcomes (KDIGO) stage, regarding clinicodemographic data, renal replacement therapy (RRT), and 90-day outcomes. Those with preexisting CKD Stage 4 (defined by estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) and above, prior renal transplant (s), or acute glomerulonephritis were excluded. The primary outcome was a composite of de novo CKD (eGFR <60 mL/min/1.73 m2) or CKD progression (decline in eGFR category to any higher stage) in patients with baseline CKD at 90 days. The secondary outcome was a composite of de novo CKD, CKD progression, or death at 90 days. Results: Of the 358 patients, 52.5% had Stage 3 AKI. Eighty-eight patients (24.6%) had baseline CKD. Sepsis (51.4%) was the predominant etiology followed by nephrotoxins (42.5%). Renal replacement therapy (RRT) was required in 94 (26.3%) patients with hemodialysis being the most common modality. After excluding lost to follow-up, 66 patients (20.3%) had the primary outcome, and 195 patients (60%) had the secondary outcome. The 90-day mortality was observed in 39.7% of patients. AKI stage (P = 0.002), baseline CKD (P = 0.000) and RRT need (P = 0.005) were significantly associated with the primary outcome, while age >60 (P = 0.018), SOFA (Sequential Organ Failure Assessment) ≥9 (P = 0.000), hypoalbuminemia (P = 0.024), baseline CKD (P = 0.000) and RRT need (P = 0.001) were associated with the secondary outcome. Conclusion: Sepsis was the dominant precipitant of AKI and a major proportion had preventable etiology. AKI severity, baseline CKD status, and RRT need were found to predict the development or progression of CKD.

Efficacy and Outcomes of CYP3A5 Genotype-Based Tacrolimus Dosing Compared to Conventional Body Weight-based Dosing in Living Donor Kidney Transplant Recipients.

Introduction: Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020). Methods: Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C0 on post-op day 4. Secondary end points included clinical outcomes and safety. Results: The proportion of subjects who achieved the target tacrolimus C0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up. Conclusion: Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity.

Hypertension- One ize does not fit all.

Although the vast majority of hypertension is "essential," some may be secondary. And, an accurate diagnosis of secondary cause of hypertension provides the treating clinician with a unique opportunity that renders dramatic response to the patient, either with pharmacologic therapy or surgery. One such secondary cause of hypertension is congenital adrenal hyperplasia due to 11 beta hydroxylase or 17 alpha hydroxylase deficiency. These inherited syndromes are caused by deficient adrenal corticosteroid biosynthesis, in which there is reduced negative feedback inhibition of cortisol and, depending on the steroidogenic pathway involved, an alteration in adrenal mineralocortiocoid and androgen secretion occurs. Here, we present, a young adult presented with hypertension, in association with hypokalemia and metabolic alkalosis, who was diagnosed with congenital adrenal hyperplasia (CAH) due to non-classical variant 11-beta hydroxylase deficiency, which responded dramatically to steroids therapy. Furthermore, we also report two new mis-sense mutations in CYP11B1 gene, a gene coding for 11-betahydroxylase enzyme.

A Rare Genetic Mutation in a Stone Former.

A 30-year-old woman with history of passage of stones since childhood presented with oliguria and pedal edema for 10 days. She had hypertension with a creatinine of 4.1 mg/dL. Evaluation showed presence of bilateral multiple renal calculi with features of chronicity of kidney disease. Metabolic work-up for nephrolithiasis turned out to be negative and eventually renal biopsy revealed features of chronic interstitial nephritis with greenish brown refractile crystals in the tubular lumen and interstitium. The possibility of dihydroxy adenine crystalline nephropathy was considered. Spectrophotometry of RBC lysates revealed decreased activity of Adenine phosphoribosyl-transferase enzyme. Gene amplification by PCR and sequential analysis identified a missense mutation in exon 3 region of APRT gene in the patient and her family members. This case report highlights the need to contemplate the diagnosis of DHA crystalline nephropathy in young patients with nephrolithiasis and the identification of a rare genetic mutation, which is being reported for the first time in India.

Diabetes mellitus and renal tubular acidosis in primary Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disease with multisystem involvement characterised by lymphocytic infiltration of exocrine glands resulting in keratoconjunctivitis sicca, xerostomia and bilateral parotid gland enlargement. Renal manifestation is characteristically chronic lymphocytic tubulointerstitial nephritis. Diabetes mellitus in Sjogren's syndrome has also been described in literature. In this article we discuss two cases of Sjogren's syndrome with diabetes mellitus and renal manifestations.

Metabolome and microbiome in kidney diseases.

Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.

Rhabdomyolysis Induced Acute Kidney Injury in Acute Myeloid Leukemia: An Unusual Association.

Rhabdomyolysis is a potentially life-threatening syndrome that causes acute kidney injury. Association of acute myeloid leukemia (AML) and myoglobin induced acute tubular necrosis (ATN) is rarely reported in the literature. Here, we report a young male who was admitted with fever of unknown origin. Diagnosed to have AML with renal failure and subsequently succumbed to illness, whose post mortem renal biopsy confirmed myoglobin induced ATN.

Membranous Nephropathy with Rapid Progression.

We report a 49-year-old man with microscopic hematuria, subnephrotic proteinuria, and rapidly progressive renal failure. His biopsy had features of PhosphoLipase A2 Receptor (PLA2R) positive membranous nephropathy with circumferential cellular crescents. Further work-up revealed IgG antiGlomerular Basement Membrane (anti-GBM) antibody titer of 188 U/mL (normal <7 U/mL). A final diagnosis of membranous nephropathy with anti-GBM disease was made. These two distinct pathological entities can occur together resulting in significant morbidity and mortality unless diagnosed early and treatment initiated promptly. Outcomes have been poor, given the nonspecific presentation and delay in diagnosis.

Post Renal Transplant Collapsing Glomerulopathy is Associated with Poor Outcomes.

INTRODUCTION: Collapsing glomerulopathy (CG) is a distinct morphologic pattern of proliferative renal parenchymal injury. It differ from focal segmental glomerulosclerosis (FSGS) by clinicopathologic pattern and its adverse outcome. The clinical significance of CG in renal allograft biopsies is not yet clear due to scant data and less occurrence of CG in renal transplant recipients. We conducted this single-center retrospective study to evaluate the prevalence, clinicopathological features, and outcome of post renal transplant CG. SUBJECTS AND METHODS: We studied 127 renal allograft biopsies performed over a period of 45 months (Jan 2015-Oct 2018). A diagnosis of CG was made if at least one glomerulus demonstrated global or segmental collapse of the glomerular capillary walls, associated marked hyperplasia, and hypertrophy of the overlying visceral epithelial cells. We analyzed clinical, biochemical, and pathological characteristics and its impact on renal allograft outcome. Statistical analysis was performed and continuous variables were expressed as means ± standard deviation (SD) or medians (interquartile range and noncontinuous data were expressed in percentage and numerical values. RESULTS: The prevalence of CG was 5.3% (7/127) of allograft biopsies. Out of the seven patients, six patients had undergone live donor transplant and one patient had undergone deceased donor renal transplant. The native kidney disease was unknown in these patients except one (IgA nephropathy). The median duration of diagnosis for CG was 17 months after transplantation (range 5-132months). Presenting symptoms were pedal edema and hypertension in 71.4% (5) patients each. All patients had proteinuria of more than 1 gm and renal allograft dysfunction and median serum creatinine of 3.05 mg/dl (1.5-4.8 mg/dl). All patients received standard triple immunosuppression. Over a period of 2-20 months, 57.14% (4) patients developed a graft failure and 43% (3) of the other patients had functioning grafts with serum creatinine of 1.5-4.2 mg/dl. CONCLUSIONS: CG presents with moderate to severe proteinuria and may lead to rapid graft dysfunction and subsequent graft failure in most of the patients.

The Role of Far Infrared Therapy in the Unassisted Maturation of Arterio-venous Fistula in Patients with Chronic Kidney Disease.

INTRODUCTION: The goal of arterio-venous fistula (AVF) creation is to achieve a well-functioning access that can be cannulated repetitively and can provide adequate flow for the dialysis. The objective of this study was to assess the role of far infrared (FIR) therapy in the unassisted maturation of newly created AVF in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: In this prospective open labeled randomised control trial, 107 patients were randomized. Participants in the control arm received oral clopidogrel 75 mg once daily for 30 days along with isometric hand exercise, whereas those in the test arm received FIR therapy twice weekly, 40 min session each, for 4 weeks. A biopsy from venous end was taken during fistula surgery. Doppler study of AVF was done at the end of the 4th and 12th week to assess AVF. Vascular access guidelines proposed by National Kidney Foundation -Kidney Disease Outcomes Quality Initiative (NKF- KDOQI) in 2006 were adapted to define the maturation of AVF. RESULTS: Out of 107 patients, 51 were randomized to the test arm and 56 to the control arm. During follow-up, the blood flow rate through AVF (Qa) and the diameter of the cephalic vein draining (CVd) the AVF were measured. At the end of 3 months, Qa in Radio-Cephalic Fistula (RCF) was high in the test arm (p-0.003). The AVF failures were 5 (10.2%) and 14 (28%) in the test and control arms, respectively (p: 0.025). However, when adjusted for AVF failure within 6 h of surgery (may be related to surgical technique) this difference in AVF patency was statistically insignificant (p: 0.121). The mean Qa was high in patients with an arterial intimal medial thickness (AIMT) <0.5 mm. The IMT of the anastomosed artery had statistically significant correlation with the primary failure rate of AVF (P < 0.001). CONCLUSION: In patients with CKD, FIR therapy was effective in increasing the AVF blood flow rate at the end of 3 months, though the difference in primary failure rate was statistically insignificant.

Influence of CYP3A5 and ABCB1 Polymorphism on Tacrolimus Drug Dosing in South Indian Renal Allograft Recipients.

INTRODUCTION: Tacrolimus blood levels are influenced by polymorphisms involving Cytochrome 3A subfamily (CYP3A5) and P-Glycoprotein (ABCB-1) genes. However, their role in transplant outcomes was less studied in South Indian population. We studied the prevalence and impact of these polymorphisms in renal transplant recipients from South India. METHODS: An analysis of CYP3A5, ABCB1 genotype done in 101 renal transplant recipients by polymerase chain reaction was correlated with blood tacrolimus trough levels (CLIA method), weight, concentration/dose (L/D) ratio, incidence of biopsy proven early acute rejections, and tacrolimus toxicity. RESULTS: Prevalence of CYP3A5*1/*1, *1/*3 and *3/*3 and ABCB1 (3435C>T) TT, CT, CC genotypes were 12 (11.9%), 48 (47.5%), 41 (40.6%) and 16 (15.8%), 45 (44.6%), 40 (39.6%), respectively. Mean tacrolimus level, median concentration/dose (L/D) ratio were significantly lower in homozygous (CYP3A5*1/*1-6.01 ng/mL; 48.99 ng/mL/mg/kg/day) and heterozygous expresser group (CYP3A5*1/*3-5.84 ng/mL; 68.93 ng/mL/mg/kg/day) when compared with nonexpresser group [CYP3A5*3/*3-7.46 ng/mL (P < 0.001);181.3 ng/mL/mg/kg/day (P < 0.05]. No significant differences observed between the ABCB1 genotypic groups. Incidence of early acute rejections (30% vs. 9.76%; P 0.016) and tacrolimus-related toxicity (14.6% vs. 5%; P 0.039) were significantly higher in CYP3A5 expressers and nonexpressers, respectively. No correlation observed between the ABCB1 polymorphisms between rejection episodes or tacrolimus renal toxicity. Among 101 patients, 40.6% were non-expressers (poor metabolizers) (*3/*3). CONCLUSIONS: CYP3A5 polymorphisms correlated with tacrolimus dose requirements and blood levels, incidence of early acute rejection, and tacrolimus nephrotoxicity. CYP3A5 polymorphism analysis prior to renal transplant will aid more precise early tacrolimus dose calculation to balance between rejection and toxicity.

Volume Assessment in Hemodialysis: A Comparison of Present Methods in Clinical Practice with Sonographic Lung Comets.

Dry weight assessment in dialysis patients remains a challenging endeavor owing to the limitations of the available methods for volume assessment. Lung ultrasound is emerging as an invaluable tool to assist in the appropriate assessment and assignment of dry weight. The objectives of this study are (1) to determine the reliability of clinical signs and symptoms for volume assessment, (2) to compare lung ultrasound with High Resolution Computed Tomography (HRCT) chest-A noninvasive gold standard tool for detecting pulmonary congestion and with inferior vena cava diameter (IVCD) - another time-tested volume assessment method, and (3) to analyze if lung ultrasound could detect dialysis induced fluid status variations. The cross-sectional study involves 50 patients on maintenance hemodialysis. Lung ultrasound for B line estimation and ultrasonographic measurement of IVCD performed before and after hemodialysis by a nephrologist trained in ultrasonography. Limited HRCT was obtained just before hemodialysis. Edema, crackles, and dyspnea had a poor sensitivity of 37.9%, 11.5%, and 52.6%, respectively, to detect clinically significant pulmonary congestion by lung ultrasound. A highly significant correlation was obtained between B-line score and HRCT signs of pulmonary congestion (P < 0.001) before dialysis. B lines showed statistically significant reduction with dialysis. The absolute reduction of B lines showed significant correlation with ultrafiltration volume and weight loss. Bedside lung ultrasound appears a sensitive tool for evaluating real-time changes in extravascular lung water and would serve to optimize volume status in dialysis patients.

Cleistanthus collinus poisoning.

Cleistanthus collinus is an extremely toxic plant poison. Cleistanthin A and B, the toxins of Cleistanthus collinus, are diphyllin glycosides which produce cardiac arrhythmias, urinary potassium wasting, hypoxia, metabolic acidosis and hypotension. We report ARDS, distal renal tubular acidosis and distributive shock secondary to inappropriate vasodilatation in a case following ingestion of its leaves.