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.

Association of IgA Nephropathy with Squamous Cell Carcinoma of the Tongue: - Case Report and Review of Literature.

A 32-year-old habitual tobacco chewer was diagnosed with squamous cell carcinoma of the tongue. He was initiated on chemo-radiation therapy. After completing 23 cycles of radiation and four cycles of cisplatin-based chemotherapy, he presented with acute nephritic syndrome. Renal biopsy showed IgA nephropathy and acute tubular injury. With supportive care, renal function stabilised with a reduction in proteinuria. We wish to highlight the poorly understood association between mucosal malignancies and IgA nephropathy. It is also interesting to note the peculiar temporal profile of glomerular involvement in our patient, where the onset of the glomerulonephritis was after the initiation of chemo-radiotherapy. This is unlike what has been described earlier.

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.

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.

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.

Lupus nephritis in a patient with retroviral infection.

A 38-year-old woman, diagnosed as Person Living with Human Immunodeficiency Virus (HIV) on Highly Active Antiretroviral Therapy (HAART) for three years, presented with features of fever, rashes, joint pain, dyspnea and pedal edema. On evaluation, a diagnosis of Systemic Lupus Erythematosus with Lupus Nephritis (LN) triggered by HIV infection was made based on clinical and serological evidence. She was continued on HAART, and immuno-suppressive therapy was co-administered resulting in the resolution of her symptoms. Lupus-like histopathological findings have been reported in patients with HIV-related kidney diseases. This case report is to highlight the co-existence of LN in a patient with HIV infection.