Drug-induced Kidney Disease: Revisited.

Drug-induced kidney disease (DIKD) is a frequent cause of acute and chronic kidney disease (CKD) that leads to high morbidity, hospitalization, and increased healthcare costs. There is a need to constantly update our knowledge in this field, given the ever-burgeoning list of newer treatments that are emerging, especially in the field of cancer immunotherapy. Generalizing the complex pathways causing DIKD from different agents, the common mechanisms include direct toxicity, immune-mediated injury, and drug-induced alterations in renal blood flow. Proper management of this condition involves risk minimization, early detection of renal damage, and timely discontinuation of potential agents to avoid irreversible renal damage.

On the earliest descriptions of the uremic syndrome in medical literature.

Uremic syndrome refers to the clinical manifestations of renal failure (acute or chronic) that results from the accumulation of several endogenous toxins normally excreted by the kidneys and can be fatal unless the primary cause is addressed and the toxins removed by dialysis. A historical description of the syndrome is traditionally believed to start in the 18th - 19th century through seminal works in the field of experimental medicine. This account, however, ignores the possibility of clinical apperception of this syndrome in ancient medical literatures. The Sushruta Samhita (SS), a Sanskrit text whose authorship is attributed to the legendary ancient Indian surgeon Sushruta (6th century BC), is well known for its pioneering descriptions of several surgical procedures, even though its contribution to the fields of internal medicine and especially nephrology is detailed. Prameha, a term that first appears in the SS, and subsequently in later historical Ayurvedic (traditional Indian medicine) texts, denotes a multi-systemic disease syndrome impacting the neurological, cardiac, dermatological, and gastrointestinal systems that is recognized through its intimate association with urinary abnormalities such as hematuria, frothy urine, or glycosuria. This construct is highly consistent with uremic syndrome originating from multiple renal disease processes such as acute glomerulonephritis, nephrotic syndrome, diabetes mellitus, etc. Furthermore, medical treatment of prameha, as detailed in the original text, reflects several recently validated approaches to managing chronic kidney disease, supporting the hypothesis that this historical entity may be one of the earliest descriptions of uremic syndrome in medical history.

A Novel Predictive Model for Hospital Survival in Patients who are Critically Ill with Dialysis-Dependent AKI: A Retrospective Single-Center Exploratory Study.

Background: Mortality of patients who are critically ill with AKI initiated on RRT is very high. Identifying modifiable and unmodifiable clinical variables at dialysis start that are associated with hospital survival can help, not only in prognostication, but also in clinical triaging. Methods: A retrospective observational study was conducted on patients with AKI-D who were initiated on RRT in the medical and surgical intensive care units (ICUs) of a high-acuity academic medical center from January 2010 through December 2015. We excluded patients with suspected poisoning, ESKD, stage 5 CKD not on dialysis, or patients with AKI-D initiated on RRT outside of the ICU setting. The primary outcome was in-hospital mortality. Results: Of the 416 patients who were critically ill with AKI-D admitted to the medical (38%), surgical (41%), and cardiac (21%) ICUs, with nearly 75% on artificial organ support, the mean age 62.1±14.8 years, mean SOFA score was 11.8±4.3, dialysis was initiated using continuous RRT in 261 (63%) and intermittent hemodialysis in 155 (37%) patients. Incidence of survival to hospital discharge was 48%. Using multivariable logistic regression with stepwise backward elimination, a prognostic model was created that included the variables age, CKD, COPD, admission, and within 24 hours of the start SOFA score, refractory hyperkalemia and uremic encephalopathy as dialysis indications, BUN >100 mg/dl, serum creatinine, serum lactate, serum albumin, CRRT as initial modality, severe volume overload, and abdominal surgery. The model exhibited good calibration (goodness of fit test, P=0.83) and excellent discrimination (optimism-corrected C statistic 0.93). Conclusions: In this single-center, diverse, critically ill AKI-D population, a novel prognostic model that combined widely used ICU scores, clinical and biochemical data at dialysis start, and dialysis indication and modality, robustly predicted short-term survival. External validation is needed to prove the generalizability of the study findings.

Regulation of Calcium Homeostasis in Acute Kidney Injury: A Prospective Observational Study.

Background: Maintaining homeostasis is an integral part of all physiological processes both in health and disease including critically ill patients and may impact clinical outcomes. The present study was designed to assess prevalence of serum calcium, phosphate, vitamin-D3, FGF-23, and PTH levels abnormalities in AKI. Patients and methods: Single-center, prospective, observational study in a tertiary care hospital. Patients meeting KDIGO criteria for AKI were included. Paired blood samples were drawn from eligible patients-first sample within 24 hours of AKI diagnosis and second after 5 days or at time of hospital discharge, whichever was earlier for measuring serum calcium (albumin corrected), phosphate, PTH, 25(OH)Vit-D, and FGF-23 levels. Clinical outcomes analyzed included survival status, utilization of RRT, and hospital stay. Results: Of the 50 patients with AKI, about three-fourths were males. Mean age of the participants was 57.32 ± 11.47 years. Around half of patients had hypocalcemia and four-fifths had low serum phosphate. Nearly 82% had low 25(OH)Vit-D and 52% cases had high PTH level. Patients who underwent RRT had numerically higher but not significant serum calcium and PTH levels. FGF-23 levels (pg/mL) were significantly higher in patients on RRT (81.70 ± 17.30 vs non-RRT, 72.43 ± 20.27, p = 0.049), nonsurvivors (87.96 ± 18.82 vs survivors 57.11 ± 15.19, p = 0.045), and those hospitalized for time of stay above median (109.67 ± 26.97 vs below median 70.27 ± 20.43, p = 0.046). Among all the bone and mineral parameters analyzed high FGF23 levels were consistently linked with poor clinical outcomes in AKI. Conclusion: The present study found high prevalence of calcium and phosphate disorders in AKI with dysregulated phosphate homeostasis as evidenced from elevated FGF-23 levels linked with morbidity and mortality in AKI. How to cite this article: Singh NP, Panwar V, Aggarwal NP, Chhabra SK, Gupta AK, Ganguli A. Regulation of Calcium Homeostasis in Acute Kidney Injury: A Prospective Observational Study. Indian J Crit Care Med 2022;26(3):302-306.

Red cell transfusion in chronic kidney disease in the United States in the current era of erythropoiesis stimulating agents.

Anemia is a major complication of chronic kidney disease (CKD) that leads to many symptoms of this disease and worsens cardiovascular health. Treatment of this condition was revolutionized three decades ago by the commercial availability of recombinant human erythropoietin which held the promise of completely eliminating the need for red blood cell transfusion (RBCT). Despite specific therapy now available for anemia in CKD, clinical data accumulated in the last 2 decades suggests that there is a continued need for RBCT, which, we surmise, is due to underutilization of Erythropoietin Stimulating Agents (ESA) or clinical settings such as active bleed, bone marrow resistance such as myelofibrosis or infections where ESAs are ineffective. The purpose of this narrative review is to highlight the adverse effects and summarize the current patterns of RBCT use in all stages of CKD while elaborating on the clinical characteristics of patients that increases their risks of transfusion exposure. We discuss, briefly, salient features of the pathophysiology of anemia in CKD and its contemporary therapies while presenting our perspectives on how to optimize transfusion strategies without compromising patient safety.

Obstructive Uropathy as an Initial Presentation of Primary Myelofibrosis: Case Report and Review of Literature.

Primary myelofibrosis (PMF) is a rare hematological disorder associated with progressive cytopenia and extra-medullary hematopoiesis. Acute kidney injury in this disease has been reported from diverse etiologies such as renal and peri-renal extramedullary hematopoiesis and tumor lysis syndrome. We report a patient who presented with obstructive uropathy from uric acid stones who was incidentally diagnosed with PMF during workup for persistent thrombocytosis and leukocytosis. Marrow histopathology was unique in presenting features of early PMF despite clinical picture mimicking essential thrombocythemia. Despite a common background of hyperuricemia in myeloproliferative neoplasms, AKI resulting from urate nephrolithiasis has seldom been reported in PMF. Published data on this association and clinical management is reviewed briefly.

Hyponatremia: incidence, risk factors, and consequences in the elderly in a home-based primary care program.

AIMS: To determine the incidence, risk factors, etiology, and associations of hyponatremia in community-dwelling elderly with geriatric morbidity and mortality. MATERIALS: Elderly participants of a single center home-based primary care program were included. METHOD: Retrospective chart review was conducted on demographic and clinical variables, comorbid diseases, frailty by Fried criteria and biochemical tests over a 1-year period. Primary outcome measure was a composite of falls, fractures due to falls, and hospitalization witnessed within the first year of enrollment into the program. Secondary outcome was all-cause mortality. RESULTS: The study population (n = 608) had a mean age of 84.3 ± 9.3 years and was largely female (77.1%) and African-American (89.5%). Mean follow-up was 41.5 months. Frailty was seen in 44.4%. Incidence of allcause mortality was 26.9%. Initial hyponatremia occurred in 8.71% (n = 53), and persistent hyponatremia (> 6 months of low serum sodium) in 4.1% (n = 25) of the study population. The major causes of hyponatremia included multiple potential causes, idiopathic syndrome of inappropriate antidiuretic hormone (SIADH) and medications (thiazides and selective serotonin reuptake inhibitor (SSRI)). Primary outcome was independently associated with frailty (Odds ratio (OR) of 2.33) and persistent but not initial hyponatremia (OR 3.52). Secondary outcome was independently associated with age > 75 years (OR 2.88) and Afro-American race (OR 2.09) only but not to frailty or hyponatremia. CONCLUSIONS: Hyponatremia is common in home-bound elderly patients and its persistence independently contributes to falls, fractures, and hospitalization but not mortality. Our study highlights a new association of hyponatremia with frailty and underscores the need to study time-dependent association of hyponatremia with epidemiological outcomes.

Kidney diseases associated with haematological cancers.

Advances in chemotherapy for haematological malignancies, resulting from a greater understanding of the complex pathophysiology of these diseases, have improved the survival of patients with these disorders. Clinicians must now, therefore, be more aware of the issues related to fluid, electrolyte, and acid-base disorders, as well as acute and chronic kidney injuries that can develop in such patients as a result of the underlying malignancy and its treatment. Patients with acute kidney injury associated with haematological malignancy have a worse prognosis than do other patients with acute kidney injury. Glomerular diseases associated with haematological malignancies are thought to be paraneoplastic syndromes with variable histological presentations. Some of the newest therapeutic agents used to treat haematological malignancies have adverse renal effects that can preclude continuation of treatment, often leading to difficult clinical decisions when patients have advanced disease and alternative treatment options are limited. Haematopoietic stem cell transplantation has an expanding role as a therapy for haematological malignancies but is also associated with important renal complications. Here, we review the literature that examines the incidences, aetiologies, mechanisms and treatment options for renal disorders associated with haematological malignancies.

Primary Sjogren's syndrome presenting as Acute Flaccid Quadriplegia:.

Primary Sjogren's Syndrome presenting as quadriplegia and respiratory involvement due to renal tubular acidosis causing hypokalemia is rare and the significance of managing such case with potassium citrate instead of potassium chloride is highlighted.

Lipid peroxidation products formation with various intravenous iron preparations in chronic kidney disease.

The role of intravenous iron in contributing to oxidative stress and endothelial dysfunction in chronic kidney disease (CKD) is debatable. The present study assessed differences in fasting plasma malondialdehyde (pMDA) levels 30 minutes before and after intravenous infusion of low molecular weight iron dextran (ID) (n = 19), iron-sucrose (IS) (n = 20), and sodium ferrigluconate complex (SFGC) (n = 20) in stage 3 and 4 CKD patients. Post-infusion pMDA levels were significantly raised with respect to baseline (p < 0.001). pMDA was significantly higher in the SFGC group vs. IS (3.02 +/- 0.84 micromol/L vs. 2.82 +/- 0.44 micromol/L, p = 0.034) or SFGC vs. ID (3.02 +/- 0.84 micromol/L vs. 2.92 +/- 0.20 micromol/L, p = 0.048). There was no difference between IS vs. ID (2.82 +/- 0.44 micromol/L vs. 2.92 +/- 0.20 micromol/L, p = 0.21). To conclude, all forms of parenteral iron, especially SFGC, significantly raise pMDA levels in the immediate post-transfusion period.

Mycophenolate mofetil or standard therapy for membranous nephropathy and focal segmental glomerulosclerosis: a pilot study.

BACKGROUND: The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding. METHODS: We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2-3 months. Conventional therapy was prednisolone 1 mg/kg/day for 3-6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio. RESULTS: A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose. CONCLUSIONS: A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster and reduces steroid exposure in FSGS patients. Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.

A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size, quality, and duration. This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine, development of ESRD, and quality of life in a randomized, controlled trial. Patients were followed up for 10 yr. Data were analyzed on an intention-to-treat basis. A total of 93 patients completed the study. Of the 47 patients who received the experimental protocol, 34 achieved remission (15 complete and 19 partial), compared with 16 (five complete, 11 partial) of 46 in the control group (P < 0.0001). The 10-yr dialysis-free survival was 89 and 65% (P = 0.016), and the likelihood of survival without death, dialysis, and doubling of serum creatinine were 79 and 44% (P = 0.0006) in the two groups. Treated patients exhibited significantly lower prevalence of edema, hypertension, hypoalbuminemia, hyperlipidemia that required therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and better quality of life on follow-up. The incidence of infections was similar in the two groups. In conclusion, untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function. A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion, arrests progression of renal insufficiency, and improves quality of life.

Nephrotic syndrome as a complication of intravesical BCG treatment of transitional cell carcinoma of urinary bladder.

Nephrotic syndrome can be associated with various neoplasms, especially solid tumors and lymphomas. This patient presented with painless hematuria of transitional cell carcinoma of urinary bladder, underwent transurethral resection, but developed recurrence 16 months later. Repeat resection was done and intravesical Bacillus Calmette-Guerin (BCG) injections were started. After six months, the patient developed hypertension and nephrotic syndrome with a biopsy revealing membranous glomerulonephritis, though there was no radiological evidence of tumor. This is the first case of nephrotic syndrome with intravesical BCG instillation in a bladder carcinoma patient.

Rare thoracic mass lesion--myofibrobastoma.

Mesenchymal soft tissue masses are uncommon tumours of the chest. Myofibroblastoma is a recently described entity consisting of cells with origin from the myoepethelial cell, mostly seen as benign well-circumscribed neoplasms of the breast tissue. Though usually classified as a benign lesion, rarely it can be multifocal and prone to recurrence. We describe below the case of a 26-year-old female who presented with exertional dyspnoea and evidence of a massive mass lesion in the left hemithorax causing mediastinal displacement to the opposite side. On histological and immunophenotypic analysis, a diagnosis of the very rare thoracic myofibroblastoma was made. The incidence, salient features, pathological differential diagnoses and treatment are reviewed.