Chronic kidney disease and vaccinations-A practical guide for primary care providers.

Patients with chronic kidney disease (CKD) are susceptible to infectious organisms in part due to the many facets of uremia-associated immune deficiency. Vaccination plays a crucial role in curbing vaccine preventable infection in patients with CKD and Kidney transplant recipients. Vaccination should be done early in the course of CKD or prior to kidney transplantation when possible. It is incumbent upon all healthcare providers to not only stay abreast of the rapidly evolving evidence and recommendations regarding this area but to also continue to update clinical practice regarding vaccines for long-recognized infectious threats, such as pneumococcal disease and chronic hepatitis B infection, to mitigate the burden of infectious diseases on this particularly vulnerable patient population.

Chronic inflammation and calciphylaxis.

Calciphylaxis also known as calcific uraemic arteriolopathy is a rare condition mostly seen in patients with end-stage kidney disease. We report a case of a simultaneous-kidney-pancreas transplant patient with functioning grafts developing biopsy-proven calciphylaxis in the setting of chronic inflammation. Despite several modalities of management, the patient developed progression of her disease leading to multiple amputations. This case illustrates chronic inflammation driven by persistent infection as a probable contributing factor to the development and progression of calciphylaxis in a simultaneous kidney-pancreas recipient. Calciphylaxis should be considered in the differential for a painful, non-healing ulcer even in the absence of common risk factors.

Posttransplant proteinuria due to Apolipoprotein E2 deposition in a kidney allograft.

Lipoprotein deposition disorders limited to the kidney and causing proteinuria are rare. We present a case of nephrotic range proteinuria presenting within 4 months after deceased donor renal transplantation in a patient with end-stage kidney disease presumed secondary to hypertension. Two transplant kidney biopsies were performed sixteen weeks after transplantation, and one year after the first biopsy, both showing lipoprotein deposits in the glomeruli, progressive focal segmental glomerulosclerosis, and effacement of visceral foot processes. The patient had a normal lipid profile. Based on previous case reports of Apolipoprotein E variants causing proteinuria in native kidneys, Apolipoprotein E genotyping was performed. Genotyping showed Apolipoprotein E2 homozygosity. This Apolipoprotein E variant has been associated with lipoprotein deposition, proteinuria, and progressive kidney disease in the native kidneys. However, this is the first case of Apolipoprotein E2 homozygosity-related kidney disease in a transplant recipient. The patient was treated with fenofibrate, angiotensin enzyme inhibition, and angiotensin receptor blockade with reduction in proteinuria, and he kept good stable kidney function.

Successful Treatment of Pembrolizumab-Induced Severe Capillary Leak Syndrome and Lymphatic Capillary Dysfunction.

Although capillary leak syndrome has a high mortality rate, its trigger, diagnosis, and treatment remain a challenge to clinicians because of the poor understanding of its mechanism and lack of treatment guidelines. With the extended use of immune checkpoint inhibitors in modern oncology, immune checkpoint inhibitor-associated immune-related adverse events have also expanded. We present a case of pembrolizumab-induced capillary leak syndrome and lymphatic capillary dysfunction in which the patient had an excellent clinical response to a tailored treatment strategy.

Impact of Subclinical and Clinical Kidney Allograft Rejection Within 1 Year Posttransplantation Among Compatible Transplant With Steroid Withdrawal Protocol.

Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.

Kidney Injury in Multiple Myeloma: A Kidney Biopsy Teaching Case.

Myeloma-related kidney disease has several manifestations; the 2 most common histologic diagnoses are myeloma cast nephropathy and acute tubular necrosis. We describe a case of different kidney pathologies occurring concomitantly in a patient found to have immunoglobulin A κ multiple myeloma. A White woman in her 70s presented with an 8-month history of back pain and was found to have nephrotic-range proteinuria and acute kidney injury. Serum calcium level was 12.6 mg/dL. Kidney biopsy showed κ light chain only proliferative glomerulonephritis with monoclonal immunoglobulin deposits, crystalglobulinemia, light chain proximal tubulopathy with κ light chain deposits, mild tubular atrophy, and interstitial fibrosis. Free κ light chain ratio was >1,000 mg/dL and free κ light chain level was 4,670 mg/dL. Within a week following treatment of hypercalcemia and initiation of chemotherapy, her acute kidney injury and hypercalcemia resolved. This case highlights the many kidney manifestations of multiple myeloma and that prompt management targeting these manifestations, including hypercalcemia, can improve clinical outcomes.

Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is known to be associated with increased mortality, and racial differences in hospital mortality exist in patients with AKI. However, it remains to be seen whether racial differences exist in post-hospitalization mortality among AKI patients. METHODS: We analyzed data of adult AKI patients admitted to the University of Virginia Medical Center between January 1, 2001, and December 31, 2015, to compare in-hospital and post-hospitalization mortality among hospitalized black and white patients with AKI. Multivariable logistic regression analysis was used to analyze the association between race and in-hospital mortality, and 90-day post-hospitalization mortality among AKI patients that were discharged. Kaplan-Meier survival curve was used to evaluate long-term survival between black and white patients. RESULTS: Black patients had lower in-hospital mortality than white patients after adjusting for age, sex, estimated glomerular filtration rate, hospital length of stay, severity of AKI, comorbidities, and the need for dialysis and mechanical ventilation (odds ratio: 0.82; 95% confidence interval, 0.70-0.96, p = 0.0015). Similarly, at 90-day post-hospitalization, black patients had significantly lower adjusted odds of death than white patients (odds ratio: 0.64; 95% confidence interval, 0.46-0.93; p = 0.008). The median length of follow-up was 11.9 months (0.6-46.7 months). Kaplan-Meier survival curve showed that long-term survival was significantly better in black patients compared to white patients (median duration of survival; 39.7 vs. 24.8 months; p ≤ 0.001). CONCLUSIONS: Black patients with AKI had lower in-hospital mortality, 90-day post-hospitalization mortality, and better long-term survival rates compared to white patients with AKI.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Clinical outcomes of solid organ transplant recipients with metastatic cancers who are treated with immune checkpoint inhibitors: A single-center analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but to the authors' knowledge, limited data exist regarding the safety and efficacy of these agents in transplant recipients. Herein, the authors have reported their experience with 17 patients who were treated with ICIs for metastatic malignancies after undergoing solid organ transplantation. METHODS: Data were abstracted for solid organ transplant recipients who received ICIs for the treatment of malignancy between January 1, 2016, and September 30, 2019. The authors identified 7 kidney, 8 liver, and 2 heart transplant recipients. Outcomes of interest were adverse drug reactions, cancer progression, and patient survival. RESULTS: The most common malignancies treated with ICIs were metastatic squamous cell carcinoma (5 patients; 29%) and hepatocellular carcinoma (5 patients; 29%), which were noted exclusively among liver transplant recipients. The median duration on ICIs was 1.7 months (interquartile range, 0.4-7.6 months). Five patients (29%) developed adverse reactions, including 4 patients (24%) with immune-related adverse events(irAEs), 3 patients (18%) with acute allograft rejections, 1 patient (6%) with autoimmune colitis, and 1 patient (6%) with ICI-induced cardiotoxicity (the patient was a heart transplant recipient). The cumulative incidence of cancer progression was 50% and 69%, respectively, at 6 months and 12 months. Eleven patients (65%) died over the median follow-up period of 4.6 months (interquartile range, 1.5-13.2 months) from the time of ICI initiation, with cancer progression being the most common cause of death. CONCLUSIONS: ICIs can be used as individualized therapy in selected patients who have undergone solid organ transplantation but more studies are needed to determine how best to use these agents to improve outcomes further.