Keddis, Mira T.

Summary Background Hospitalized patients with hyperkalemia are heterogeneous, and cluster approaches may identify specific homogenous groups. This study aimed to cluster patients with hyperkalemia on admission using unsupervised machine learning (ML) consensus clustering approach, and to compare characteristics and outcomes among these distinct clusters. Methods Consensus cluster analysis was performed in 5133 hospitalized adult patients with admission hyperkalemia, based on available clinical and laboratory data. The standardized mean difference was used to identify each cluster’s key clinical features. The association of hyperkalemia clusters with hospital and 1-year mortality was assessed using logistic and Cox proportional hazard regression. Results Three distinct clusters of hyperkalemia patients were identified using consensus cluster analysis: 1661 (32%) in cluster 1, 2455 (48%) in cluster 2 and 1017 (20%) in cluster 3. Cluster 1 was mainly characterized by older age, higher serum chloride and acute kidney injury (AKI), but lower estimated glomerular filtration rate (eGFR), serum bicarbonate and hemoglobin. Cluster 2 was mainly characterized by higher eGFR, serum bicarbonate and hemoglobin, but lower comorbidity burden, serum potassium and AKI. Cluster 3 was mainly characterized by higher comorbidity burden, particularly diabetes and end-stage kidney disease, AKI, serum potassium, anion gap, but lower eGFR, serum sodium, chloride and bicarbonate. Hospital and 1-year mortality risk was significantly different among the three identified clusters, with highest mortality in cluster 3, followed by cluster 1 and then cluster 2. Conclusion In a heterogeneous cohort of hyperkalemia patients, three distinct clusters were identified using unsupervised ML. These three clusters had different clinical characteristics and outcomes.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy characterized by renal loss of calcium and magnesium leading to progressive renal failure. The disorder is caused by variants to the tight junction proteins claudin-16 and -19. While rare, this disorder causes a significant burden to patients based on its clinical manifestations of various electrolyte abnormalities, nephrocalcinosis, and early progression to renal failure. In this report we describe the diagnosis of a novel variant of CLDN16 which clinically presented with severe hypomagnesemia, hypocalcemia, nephrocalcinosis, and renal failure.

Introduction: End stage renal disease (ESRD) patients with concomitant heart failure (HF) are often denied kidney transplantation (KTx). The aims of this study were to explore factors predictive of suitability for KTx and to assess cardiovascular (CV) outcomes in patients with impaired left ventricular ejection fraction (LVEF) presenting for KTx evaluation. Methods: We evaluated 109 consecutive adults with LVEF≤40% at the time of initial KTx evaluation between 2013 and 2018. Post-transplant CV outcomes were defined as non-fatal MI, admission for HF, CV death and all-cause mortality. Results: Mean age was 58.2 years (SD11.9), 78% were male, 58% had diabetes, 70% had history of CV events and 42% had ischemic cardiomyopathy. Mean LVEF was 31.5% (SD 6.47). Eighty patients had nuclear stress imaging; 10% were positive for reversible ischemia and 43% for prior infarct. Mean VO2max was 14.4(SD 5.71)ml/kg/min (31 patients). A cardiologist evaluated 93% of patients and was present at 58% of selection committee meetings. Twenty-four patients (22%) were denied by a cardiologist for KTx and 59 (54%) were denied by the selection committee, of whom 43 were due to CV risk. On univariate analysis, the variables associated with denial for KTx were: cardiologist denial, denial due to CV risk, Native American race (6% of cohort), higher NT-pro-BNP, prior MI, coronary intervention, positive stress study, anemia, lower EF and lower VO2max (all p<0.05). On multivariate analysis, cardiologist denial was the only significant predictor of denial for KTx (OR: 29.4, p=0.0007). At median follow-up of 15 months, 5 (5%) suffered non-fatal MI, 13 (12%) were hospitalized for HF exacerbation and 17 (16%) died. Only 22 (20%) underwent KTx. Post-KTx, there was one death, one non-fatal MI and 3 hospitalizations for HF. Mean LVEF improvement was 16% (SD12.9). Conclusions: Only 38% of ESRD patients with LVEF≤40% presenting for KTx evaluation were approved and of those, only 52% received KTx. Cardiologist approval was the primary predictor of suitability for KTx. Despite careful selection, prevalence of CV events and mortality after KTx was 23%. There is need for a consistent multidisciplinary approach during KTx evaluation, including cardiologist input, to improve CV outcomes.

Objective Native Americans suffer from lower rates of kidney transplantation compared with whites. Our goal was to elicit patients’ perceptions of and attitudes about kidney transplant and the impact of financial burden and cultural taboos. Design This is an exploratory qualitative interview study of 12 Native American patients recruited after completion of the kidney transplant evaluation. Setting Semistructured interviews were conducted. Interviews were coded using inductive methods, followed by interpretive coding by the investigators. Results Thematic analysis revealed the following themes: (1) experience with kidney transplant education by the healthcare team; (2) cultural beliefs regarding kidney transplant; (3) personal motivation and attitude towards kidney transplant; (4) financial burden of kidney transplant and post-transplant care and (5) attitude about living donation. Most participants were educated about transplant as a treatment option after dialysis initiation. All patients in this study recognised that some taboos exist about the process of organ procurement and transplantation; however, the traditional views did not negatively impact their decision to pursue kidney transplant evaluation. Patients shared the common theme of preferring an organ from a living rather than a deceased person; however, the majority did not have a living donor and preferred not to receive an organ from a family member. Most patients did not perceive transplant-related cost as negatively impacting their attitude about receiving a transplant even for patients with below poverty level income. Conclusions Native American patients presenting for kidney transplant were less likely to be educated about transplant before dialysis initiation; did not perceive financial burden and cultural beliefs were not discussed as obstacles to transplant. While a living donor was the preferred option, enthusiasm for living donation from family members was limited.

Background Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO 2peak ), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. Methods and Results We outlined a pre–renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all‐cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. Conclusions We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

AbstractBackgroundSkin cancer prevalence is well‐characterized for white solid organ transplant recipients. Although the prevalence of skin cancer in non‐white (Black, Asian, Hispanic) kidney transplant recipients (KTRs) has been assessed, no study has reported the prevalence of skin cancer in Native American (NA) KTRs. The aim of this study is to determine if the prevalence of skin cancer in NAKTRs is the same as in white KTRs.MethodsWe conducted a case‐controlled retrospective review from a single transplant center. One hundred thirteen NAKTRs who received a transplant between 2001 and 2011 were age‐ and transplant‐year matched with 113 white controls.ResultsThe 226 KTRs consisted of 141 (62.4%) men and 85 (37.6%) women, with a mean age of 50.2 ± 10.8 years. There was no skin cancer found in NAKTRs prior to or post transplantation, while seven (6.2%) white KTRs had eight skin cancers prior to transplantation, and 28 (24.8%) white KTRs developed 66 skin cancers post transplantation. Twenty‐two (19.5%) NAKTRs did not follow‐up with dermatology at this institution. The median follow‐up in NAKTRs was 3.3 years compared to 3.0 years in white KTRs.ConclusionNAKTRs have a decreased prevalence of skin cancer compared to their white counterparts.

Background and objectives eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors. Design, setting, participants, & measurements A cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined. Results Median measured GFR was 55.0 ml/min per 1.73 m 2 . eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by −13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by −8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C. Conclusions Thus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.

AbstractVitamin D deficiency is common among patients with end‐stage liver disease (ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT.MethodsWe retrospectively studied 190 patients at our center. Serum total 25‐hydroxyvitamin D (25‐OH D), parathyroid hormone (PTH), calcium, and bone mineral analysis (BMA) were recorded. Standard World Health Organization (WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed.ResultsThirty‐two of 190 patients were excluded from the final analysis (missing serum total 25‐OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25‐OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25‐OH D levels: 0–10 ng/mL (n = 23), 11–20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25‐OH D ≤ 10 ng/mL had higher model for end‐stage liver disease (MELD) scores vs. those with 25‐OH D > 20 ng/mL (13.3 ± 3, range 8–21, vs. 11.9 ± 3.4, range 6–29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients.ConclusionLow vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25‐OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25‐OH D and vitamin D‐binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD.

Although renal failure is one of the known comorbidities associated with rapid progression of aortic stenosis, it is unclear whether hemodialysis alters the progression of prosthetic aortic valve stenosis. We describe a 79-year-old female who underwent bioprosthetic aortic valve replacement 8 years ago with stable prosthetic valve area for the initial 6 years. In the last two years, coinciding with the initiation of maintenance hemodialysis, she developed progressive prosthetic valve stenosis to the point of clinical decompensation. She underwent a second prosthetic aortic valve replacement with symptom resolution. This case suggests that circulating milieu in end-stage renal failure and dialysis can accelerate the progression of prosthetic aortic valve stenosis. More frequent clinical followup and surveillance echocardiogram for dialysis patients with bioprosthetic aortic valve may facilitate timely management of valvular stenosis.