Association of Proton Pump Inhibitor Use and Immune Checkpoint Inhibitor Mediated Acute Kidney Injury: A Meta-Analysis and a Review of Related Outcomes.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they pose the risk of immune-related adverse events, including ICI-mediated acute kidney injury (ICI-AKI). Recent studies have implicated proton pump inhibitors (PPIs) as potential contributors to ICI-AKI development. This meta-analysis examines the association between PPI use and ICI-AKI, exploring a potential modifiable risk factor in ICI therapy, while also reviewing the possible outcomes of ICI-AKI. METHODS: We conducted a comprehensive systematic review and meta-analysis of observational studies, assessing the risk of ICI-AKI in cancer patients concurrently using PPIs and potential outcomes. Odds ratios (ORs) were pooled using random-effects models. Subgroup analyses and sensitivity analyses were performed to evaluate heterogeneity and potential biases. RESULTS: A total of 14 studies involving 12,694 patients were included. In total, we analyzed 639 patients with all-cause AKI and 779 patients with ICI-AKI. The pooled OR for the overall incidence of AKI from all-cause was 1.57 (95% Confidence Interval (CI), 1.02 to 2.40) among patients on PPIs. Specifically, the risk of ICI-AKI associated with PPI use was significantly higher, with a pooled OR of 1.84 (95% CI 1.16 to 2.90). This indicates approximately 84% higher likelihood of developing ICI-AKI with concurrent use of PPIs. Additionally, among patients with ICI-AKI, 67% had complete or partial recovery of renal function, 32% progressed to chronic kidney disease (CKD) and about 36% died during a follow-up period of at least 3 months. CONCLUSION: This meta-analysis highlights the importance of cautious PPI prescription in cancer patients undergoing ICI therapy. Clinicians are advised to evaluate the risks and benefits of PPI use and consider alternative therapies when feasible.

Improvement in Kidney Function after Discontinuation of Fenofibrate in Outpatient Nephrology Consultation for Chronic Kidney Disease.

BACKGROUND: It has been noted in observational and interventional studies that individuals exposed to fenofibrate can exhibit a rise in serum creatinine (sCr) concentration. However, it is not known to what extent this phenomenon impacts kidney function in patients who are referred to a nephrology clinic for consultation for chronic kidney disease (CKD). METHODS: We conducted a prospective observational study of patients referred to our nephrology clinic for a new evaluation of a rise in sCr or worsening CKD and who were on fenofibrate therapy. We examined the effect of discontinuation of fenofibrate on kidney function, change in sCr, and estimated glomerular filtration (eGFR) at 3, 6, and 12 months. RESULTS: A total of 22 patients (59% women, 86% White, 59% with type 2 diabetes, and 18% with peripheral arterial disease) were captured over 2.5 years. Median sCr at the time of fenofibrate discontinuation was 1.9 (1.1-3.3) mg/dL and eGFR, 32 (17-57) mL/min; proteinuria was absent in 17 (77%). Upon discontinuation of fenofibrate, median sCr decreased to 1.5 (0.9-2.4), 1.4 (1.0-2.5), and 1.4 (1.0-2.3) mg/dL at 3, 6, and 12 months, respectively (p < 0.05); whereas median eGFR increased to 44 (27-71), 45 (23-71), and 42 (21-71) mL/min, respectively (p < 0.05). A ≥30% rise in eGFR was observed in 59% of the patients at 3 months, and it persisted in 45% and 50% of patients at 6 and 12 months, respectively. CONCLUSION: Discontinuation of fenofibrate in patients referred for CKD evaluation can result in sustained reduction in sCr in about half of the patients and for up to 1 year. There is a need to raise awareness among primary practitioners about this phenomenon. Recognition of fenofibrate as a cause of rise in sCr could reduce unnecessary nephrology consultation and resource utilization.

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma.

INTRODUCTION: Oncogenic osteomalacia (Onc-Ost) is a paraneoplastic phenomenon characterized by hypophosphatemia due to elevated fibroblast growth factor-23 (FGF-23). Onc-Ost has been previously reported in patients with germ line mesenchymal tumors and solid organ malignancies. This is the first report of aggressive natural killer (NK) T-cell lymphoma presenting as Onc-Ost. CASE DESCRIPTION: A 33-year-old Vietnamese female with active hepatitis B and Mycobacterium avium complex, on ongoing therapy with tenofovir disoproxil, azithromycin, and ethambutol, presented with persistent fevers and developed refractory hypophosphatemia. Workup confirmed severe renal phosphate wasting. Tenofovir disoproxil was initially suspected; however, presence of isolated phosphaturia without Fanconi syndrome and persistence of hypophosphatemia despite discontinuation of medication led to clinical suspicion of Onc-Ost. Elevated FGF-23 warranted further workup, leading to a definitive diagnosis of clinically subtle NK T-cell lymphoma. Chemotherapy was initiated; however, patient continued to deteriorate clinically and expired. CONCLUSION: Along with commonly reported germ line mesenchymal tumors and solid malignancies, NK T-cell lymphoma can also present as Onc-Ost. Timely detection of associated tumors and subsequent antitumor therapy would likely reverse hypophosphatemia and improve clinical outcomes.

Risk Factors and Management of Osteoporosis Post-Transplant.

Bone and mineral disorders are common after organ transplantation. Osteoporosis post transplantation is associated with increased morbidity and mortality. Pathogenesis of bone disorders in this particular sub set of the population is complicated by multiple co-existing factors like preexisting bone disease, Vitamin D deficiency and parathyroid dysfunction. Risk factors include post-transplant immobilization, steroid usage, diabetes mellitus, low body mass index, older age, female sex, smoking, alcohol consumption and a sedentary lifestyle. Immunosuppressive medications post-transplant have a negative impact on outcomes, and further aggravate osteoporotic risk. Management is complex and challenging due to the sub-optimal sensitivity and specificity of non-invasive diagnostic tests, and the underutilization of bone biopsy. In this review, we summarize the prevalence, pathophysiology, diagnostic tests and management of osteoporosis in solid organ and hematopoietic stem cell transplant recipients.

Acute Kidney Injury in Patients with Liver Disease.

AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.

A Rare Case of Patiromer Induced Hypercalcemia.

Patiromer is a calcium (Ca)-potassium (K) exchange resin approved for the treatment of hyperkalemia. Disorders of Ca or acid base balance were not reported in pre-approval clinical trials. We present a case of a patient with chronic kidney disease (CKD) with an unusual picture of hypercalcemia, metabolic alkalosis and hypokalemia upon intensification of patiromer dosing. A 56-year-old white man with CKD stage 4 (baseline creatinine 2.8 mg/dL) due to type 1 diabetes mellitus, proteinuria (1.5 g/g) and persistently high serum potassium 5.9 mEq/L attributed to type 4 renal tubular acidosis was evaluated in clinic. Due to high risk of CKD progression, patiromer 8.4 g daily, followed by 16.8 g daily was prescribed to enable renin angiotensin aldosterone system (RAAS) inhibitor. After 5 months of being on patiromer 16.8 g daily, routine laboratory tests revealed serum potassium 2.5 mEq/L, serum calcium 12.8 mg/dL and carbon dioxide 34 mEq/L. Patiromer was discontinued and thorough investigation held was negative for other causes of hypercalcemia. Five days after patiromer discontinuation, serum calcium returned to normal. The role of secondary hyperparathyroidism in this case remains unclear. We, therefore recommend cautious vigilance of patients receiving patiromer and undergoing dose escalation.

Multiple Myeloma, Hyperviscosity, Hemodialysis Filter Clogging, and Antigen Excess Artifact: A Case Report.

Kidney involvement in multiple myeloma can result in kidney failure. Unlike Waldenström macroglobulinemia, hyperviscosity syndrome is a rare occurrence in multiple myeloma. Timely detection of hyperviscosity syndrome and initiation of plasma exchange to remove paraproteins can significantly alter the clinical course and be potentially lifesaving. We report a case of hospitalized patient with kidney failure due to multiple myeloma not in remission who experienced shortened hemodialysis sessions due to early dialysis filter failure due to hyperviscosity, which was later corrected with plasmapheresis. When confirmation of high levels of serum free light chains (sFLCs) was attempted, sFLC was initially reported as "not detectable." This false-negative result reflected a laboratory artifact caused by a high abundance of sFLCs, known as antigen excess or hook phenomenon. Manual serial dilutions led to unmasking of markedly elevated κ light chain levels. This case exemplifies that patients with multiple myeloma can exhibit clinically challenging kidney manifestations even after becoming dialysis dependent.

Industry Payments to Nephrologists in the United States.

Background Industry payments to physicians raise concerns about conflicts of interest that have the potential to impact patient care. In this study, we explored nonresearch and nonownership payments from industry to nephrologists to identify trends in compensation. Methodology Using data from the Centers for Medicare and Medicaid Services (CMS), we explored financial relationships between industry and US nephrologists from 2014 to 2018. We analyzed payment characteristics including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Results In this retrospective study, a total of $75,174,999 was paid to nephrologists in the United States during the study period (i.e., 2014-2018). The number of board-certified nephrologists receiving payment from the industry increased from 11,642 in 2014 to 13,297 in 2018. Among board-certified nephrologists, 56% to 63% received industry payments during the study period. The total payments to nephrologists increased from $13,113,512 in 2014 to $16,467,945 in 2017, with consulting fees (24%) and compensation for services other than consulting (35%) being the highest-paid categories. The top 10% of physician beneficiaries collected 90% of the total industry payments. Conclusions A small proportion of US nephrologists consistently received the majority of industry payments, the value of which grew over the study period.

Kidney Recovery From Acute Kidney Injury After Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

Patients with the recovery of kidney function after an episode of acute kidney injury (AKI) have better outcomes compared to those without recovery. The current systematic review is conducted to assess the rates of kidney function recovery among patients with AKI or severe AKI requiring kidney replacement therapy (KRT) within 100 days after hematopoietic stem cell transplant (HSCT). Methods The Ovid MEDLINE, EMBASE, and Cochrane databases were systemically searched from database inceptions through August 2019 to identify studies reporting the rates of recovery from AKI after HSCT. The random-effects and generic inverse variance methods of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. Results A total of 458 patients from eight cohort studies with AKI after HSCT were identified. Overall, the pooled estimated rates of AKI recovery among patients with AKI and severe AKI requiring KRT within 100 days were 58% (95%CI: 37%-78%) and 10% (95%CI: 2%-4%), respectively. Among patients with AKI recovery, the pooled estimated rates of complete and partial AKI recovery were 60% (95%CI: 39%-78%) and 29% (95%CI: 10%-61%), respectively. There was no clear correlation between study year and the rate of AKI recovery (p=0.26). Conclusion The rate of recovery from AKI after HSCT depends on the severity of AKI. While recovery is common, complete recovery is reported in about two-thirds of all AKI patients. The rate of recovery among those with AKI requiring renal replacement therapy (RRT) is substantially lower.

Outcomes of COVID-19 in Solid Organ Transplants.

The novel coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of people worldwide. Solid organ transplant (SOT) recipients are probably at higher risk of severe infection and associated complications from COVID-19. Data on clinical outcomes of COVID-19 infection in SOT recipients are limited. Using the TriNetX database, patients with laboratory-confirmed COVID-19 from January 20, 2020, to July 7, 2020, were included in the study. We compared clinical outcomes comprising hospitalization, need for critical care services, intubation, and mortality among SOT recipients and patients without SOT. Of 30,573 laboratory-confirmed COVID-19 patients, 288 had SOT. Patients with SOT were more likely to be hospitalized (37.2% vs. 12.2%; p < 0.0001), needed critical care services (6.9% vs. 2.3%; p < 0.0001), needed intubation (7.9% vs. 2.0%; p < 0.0001), and had a higher 30-day mortality (11.1% vs. 3.8%; p < 0.0001). Patients in the transplant group were older (55.4 vs. 47.6 years; p < 0.0001) and had a higher prevalence of medical co-morbidities. SOT recipients are at significant risk of adverse COVID-19 related outcomes, including hospitalization, need for critical care services, and 30-day mortality, likely due to multiple co-morbid conditions.