Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

ß2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

bDMARD can prevent the progression of AA amyloidosis to end-stage renal disease.

INTRODUCTION: AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure. MATERIALS AND METHODS: This study is a monocentric retrospective analysis of the renal outcome and survival of patients with cid+AA (n=34), auto+AA (n=24) and idio+AA (n=25) who were treated with cytokine-inhibiting biological disease-modifying antirheumatic drugs (bDMARDs). RESULTS: 83 patients with renal AA were identified and followed for a mean observational period of 4.82 years. C reactive protein (CRP), serum amyloid alpha and proteinuria were significantly reduced with bDMARD therapy. Progression to ESRD was prevented in 60% (cid+AA), 88% (auto+AA) and 81% (idio+AA) of patients. Tocilizumab was given to 34 patients with cid+AA and idio+AA and was more effective in reducing CRP and progression to ESRD and death compared with other bDMARDs. CONCLUSIONS: bDMARDs reduce systemic inflammation in various diseases, leading to a reduction of proteinuria and prevention of ESRD. Importantly, tocilizumab was more effective than other bDMARDs in controlling systemic inflammation in patients with chronic inflammatory diseases and idiopathic AA, leading to better renal and overall survival.

End-Stage Kidney Disease After Partial and Radical Nephrectomy Among Patients With Severe Chronic Kidney Disease.

PURPOSE: AUA guidelines prioritize nephron sparing in patients with preexisting chronic kidney disease (CKD). However, few studies analyze long-term renal function in patients with preoperative severe CKD who undergo extirpative renal surgery. Herein, we compare the hazard of progression to end-stage kidney disease (ESKD) following partial nephrectomy (PN) and radical nephrectomy (RN) among patients with preoperative severe CKD. MATERIALS AND METHODS: Patients with stage 4 CKD who underwent PN or RN from 1970 to 2018 were identified. A multivariable Fine-Gray subdistribution hazard model was employed to assess associations with progression to ESKD accounting for the competing risk of death. RESULTS: A total of 186 patients with stage 4 CKD underwent PN (n = 71; 38%) or RN (n = 115; 62%) for renal neoplasms with median follow-up of 6.9 years (interquartile range 3.8-14.1). On multivariable analyses adjusting for competing risk of death, the subdistribution hazard ratio (SHR) for older age at surgery (SHR for 5-year increase 0.81; 95% CI 0.73-0.91; P < .001) and higher preoperative estimated glomerular filtration rate (SHR for 5-unit increase 0.63; 95% CI 0.47-0.84; P = .002) was associated with lower hazard of progression to ESKD. There was no significant difference in hazard of ESKD between PN and RN (SHR 0.82; 95% CI 0.50-1.33; P = .4). CONCLUSIONS: Among patients with preoperative severe CKD, higher preoperative estimated glomerular filtration rate was associated with lower hazard of progression to ESKD after extirpative surgery for renal neoplasms. We did not observe a significant difference in overall hazard for developing ESKD between PN and RN.

The Association of Class I and II Human Leukocyte Antigen Serotypes With End-Stage Kidney Disease Due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease.

RATIONALE & OBJECTIVE: Membranoproliferative glomerulonephritis (MPGN), encompassing several distinct diseases, is a rare but significant cause of kidney failure in the United States. The potential etiologies of MPGN are unclear, but prior studies have suggested dysregulation of the alternative complement pathway and, recently, autoimmunity as potential mechanisms driving MPGN pathogenesis. In this study, we examined HLA associations with end-stage kidney disease (ESKD) due to MPGN and dense deposit disease (DDD) in a large racially and ethnically diverse US-based cohort. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: Using US Renal Data System (USRDS) and United Network for Organ Sharing (UNOS) data, we identified 3,424 patients with kidney failure due to MPGN and 263 due to DDD. We matched patients to kidney donor controls on designated race and ethnicity in a 1:15 ratio. EXPOSURE: 58 class I and II HLA serotypes. OUTCOME: Case-control status. ANALYTICAL APPROACH: For each disease cohort, univariable and multivariable logistic regression analyses were used to investigate associations between the disease and 58 HLA serotypes. In subgroup analyses, we investigated HLA associations in White and Black patients. We also studied antiglomerular basement membrane (anti-GBM) nephritis as a positive-control outcome. We applied a Bonferroni correction to account for multiple comparisons. RESULTS: Eighteen serotypes were significantly associated with the odds of having MPGN in univariable analyses, with DR17 having the strongest association (odds ratio [OR], 1.55 [95% CI, 1.44-1.68], P=4.33e-28). No significant associations were found between any HLA serotype and DDD. Designated race-specific analyses showed comparable findings. We recapitulated known HLA associations in anti-GBM nephritis. LIMITATIONS: Reliance on HLA serotypes (rather than genotype), lack of biopsy-confirmed diagnoses. CONCLUSIONS: HLA-DR17 is associated with ESKD due to MPGN in a racially and ethnically diverse cohort. The strength of association was similar in White and Black patients, suggesting a role in the pathogenesis of MPGN. No HLA associations were observed in patients with DDD. PLAIN-LANGUAGE SUMMARY: Prior studies have suggested dysregulation of the alternative complement pathway as a potential etiology of membranoproliferative glomerulonephritis (MPGN), but recent evidence from a British White population has implicated an autoimmune mechanism in MPGN pathogenesis. We investigated HLA associations between MPGN and dense deposit disease (DDD) in a large racially and ethnically diverse cohort of patients. We found that HLA-DR17 is associated with end-stage kidney disease (ESKD) due to MPGN in both White and Black patients. By contrast, no significant HLA associations with ESKD due to DDD were identified. These results suggest a role for autoimmunity in some cases of MPGN and highlight differences in the disease etiology of MPGN compared with DDD.

Creating hemodialysis autogenous access in children and adolescents.

OBJECTIVE: End-stage renal disease (ESRD) in childhood and adolescence is rare, with relatively few published reports of pediatric ESRD vascular access. This study analyzes a 10-year experience creating arteriovenous fistulas (AVFs) in children and adolescents. Our goal is to review our strategy for creating functional autogenous vascular access in younger patients and report our results. METHODS: We retrospectively reviewed data and outcomes for consecutive vascular access patients aged ≤19 years during a 10-year period. Each patient had preoperative vascular ultrasound mapping by the operating surgeon in addition to physical examination. A distal forearm radiocephalic AVF was the first access choice when feasible, and a proximal radial artery inflow AVF was the next option. Demographic data, inflow artery, venous outflow target, and required transposition vs direct AVFs were variables included in the analysis. Primary and cumulative patency were calculated by Kaplan-Meier analysis. RESULTS: Thirty-seven AVFs were created in 35 patients. No grafts were used. Ages were 6 to 19 years (mean, 15 years), and 20 were male. Causes of ESRD included glomerular disease (n = 18) and urinary obstruction or reflux (n = 7), among others. Three had previous AVFs, and 10 were obese. The proximal radial artery supplied AVF inflow in 25 patients and the brachial artery in only seven. Eleven individuals required a transposition and one a vein translocation to the contralateral arm. No patients developed hand ischemia, although two later required banding procedures for high flow. Eleven patients had successful transplants. A single patient died, unrelated to the vascular access. Five AVFs failed. Of these, two had new successful AVFs created, two regained renal function, one was transplanted, and one declined other procedures. Primary and cumulative patency rates were 75% and 85% at 12 months, 70% and 85% at 24 months, and 51% and 85% at 36 months, respectively. Median follow-up was 16 months. CONCLUSIONS: Creating an AVF for hemodialysis is a successful vascular access strategy for pediatric and adolescent patients. Proximal radial artery AVFs provided safe and functional access when a distal AVF was not feasible. Cumulative AVF patency was 85% at 36 months.

Slowly moving the needle away from Fistula First.

OBJECTIVE: In 2019, the management of end-stage kidney disease (ESKD) shifted away from "Fistula First" (FF) to "ESKD Life-Plan: Patient Life-Plan First then Access Needs." Indeed, some patients exhibit such excessive comorbidity that even relatively minor vascular surgery may be complicated. The purpose of this study was to retrospectively assess complications and mortality (and delineate operative futility) in patients undergoing arteriovenous fistula (AVF) creation in the FF era. METHODS: Consecutive AVFs created in a single institution before 2021 were retrospectively reviewed. Operative futility was defined as never-accessed fistula, no initiation of dialysis, failure of access maturation (despite secondary intervention), hemodialysis access-induced distal ischemia requiring ligation, early loss of secondary patency, and/or patient mortality within the first 6 postoperative months. RESULTS: A total of 401 AVFs were created including radial-cephalic (44%), brachial-cephalic (41%), and brachial-basilic (15%) constructions. Patients exhibited a mean age of 69 ± 15 years; 63% were male, and most (74%) were already being hemodialyzed at the time of fistula creation. Forty-five patients (11%) suffered a cardiac event, and five patients died (1%) within 90 days of their access surgery. Perioperative cardiac events were significantly more common after age 80 (19% vs 8%; P = .004); age >80 years was an independent predictor of major 90-day complications (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.04-3.39; P = .036) and the sole independent predictor of major morbidity defined as cardiopulmonary complications, stroke, or death within the first year (OR, 2.01; 95% CI, 1.24-3.25; P = .004). Operative futility was encountered in 52% of the cohort (n = 208 patients): 40% (n = 160) of primary AVFs failed to mature despite assistance, 19% (n = 77) had lost secondary patency by 6 months, 13% of patients (n = 53) were never started on dialysis after access creation, 4% (n = 16) were dead by 6 months, 2% of AVFs (n = 10) matured but were never accessed, and 2% (n = 9) required ligation for hemodialysis access-induced distal ischemia. Not surprisingly, the sole independent protector against operative futility was that catheter-based dialysis had been established prior to AVF creation (OR, 0.36; 95% CI, 0.22-0.59; P < .01). CONCLUSIONS: Approximately 50% of primary AVF operations performed in the aggressive FF era were deemed futile. Octogenarians were particularly prone to futility and complications during this era. A paradigm shift, from FF to an "ESKD Life-Plan" will, hopefully, more thoughtfully match vascular access strategies to individual patient needs.

Clinical Implications of C2 Lesion in IgA Nephropathy: A Cohort Study.

INTRODUCTION: In 2016, the Oxford Classification of IgA nephropathy (IgAN) updated its scoring system for the glomerular crescents. Despite this, the clinical significance of crescentic lesions in the updated Oxford classification is still unexplored through prospective cohort studies. METHODS: 134 patients diagnosed with IgAN accompanied with C2 lesions at Peking University First Hospital were consecutively enrolled and prospectively followed up for analysis. Multivariate Cox regression in combination with LASSO regression was used to analyze risk factors associated with end-stage kidney disease (ESKD). RESULTS: During biopsy, the mean estimated glomerular filtration rate (eGFR) was 39.3 mL/min/1.73 m2, and the mean proteinuria was 4.4 g/day. The proportion of kidney failure at 1 year, 2 years, and 3 years were 24%, 34%, and 47%, respectively. The results of LASSO in combination with Cox regression showed that mean arterial pressure (hazard ratio [HR] = 1.035, 95% confidence interval [95% CI] 1.013-1.056, p = 0.001), eGFR at biopsy (HR = 0.968, 95% CI [0.948-0.990], p < 0.004) and T2 lesions (HR = 2.490, 95% CI [1.179-5.259], p = 0.017) were independent risk factor associated with ESKD in patients with C2 lesions. Furthermore, based on univariate analyses, we found that patients with kidney function declined more than 50% within 3 months prior to biopsy or pathological findings indicated a proportion of crescents exceeding 50% were both associated with a poor kidney prognosis. Lastly, when the proportion of the crescent was less than 50%, patients receiving combined steroid and immunosuppressant treatment did not exhibit a better renal prognosis than those receiving steroid only. CONCLUSION: Patients diagnosed with IgAN and concurrent C2 lesions exhibited a poor clinical prognosis, necessitating more effective treatment strategies.

Long-term outcome of kidney function in patients with ANCA-associated vasculitis.

BACKGROUND: Kidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV. METHODS: The dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995-2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs. RESULTS: The cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years.In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P < .001 and P = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71-0.83). CONCLUSIONS: Early diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome.

Referral and evaluation for kidney transplantation among patients with lupus nephritis-related end-stage kidney disease.

OBJECTIVE: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The study's objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. METHODS: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. RESULTS: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR: <1 to 11.7 months), which is similar to patients with other-ESKD (median 2.6 months, IQR: <1 to 8.8 months). CONCLUSIONS: Among incident patients with ESKD, having a primary diagnosis of LN-ESKD versus other-ESKD is associated with higher rates of early transplant access outcomes. Despite this, patients with LN-ESKD (vs other-ESKD) are less likely to be preemptively referred (i.e., referred prior to ESKD start) for kidney transplant. While providers may no longer be delaying the early steps in the kidney transplantation process among this patient population, there is still room for improvement in the rates of preemptive referral. Access to kidney transplant referral prior to ESKD could result in increased transplant rates and better transplant outcomes for patients with LN-ESKD.

Association between urinary C4d levels and disease progression in IgA nephropathy.

BACKGROUND: C4d mesangial deposition, a hallmark of lectin pathway activation in immunoglobulin A nephropathy (IgAN), has been shown to be associated with risk of kidney failure. To date, the relationship between urinary C4d and renal outcome remain unelucidated. METHODS: A total of 508 patients with biopsy-proven IgAN were enrolled in this study, whose baseline urine samples at the time of biopsy were collected and the levels of urinary C4d were quantified by enzyme-linked immunosorbent assay. The time-averaged C4d (TA-C4d) and the change in proteinuria were measured in sequential urine samples obtained from IgAN patients. The kidney progression event was defined as a 50% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease or death. RESULTS: After a median follow-up of 36 months, 70 (13.8%) of the participants reached the kidney progression event. Higher levels of urinary C4d/Ucr were found to be associated with decreased eGFR, massive proteinuria, lower serum albumin levels, hypertension, and severe Oxford E and T scores. Upon adjusting for traditional risk factors (including demographics, eGFR, proteinuria, hypertension, Oxford pathologic score and immunosuppressive therapy), elevated levels of urinary C4d/Ucr were independently associated with an increased risk of chronic kidney disease progression [adjusted hazard ratio (HR) per standard deviation increment of log-transformed C4d/Ucr: 1.46; 95% CI 1.04-2.06; P = .030]. In reference to the low C4d group, the risk of poor renal outcome increased for the high C4d group (adjusted HR 1.93; 95% CI 1.05-3.54; P = .033). Additionally, a low baseline C4d level was independently associated with a favorable proteinuria response to immunosuppressive therapy at 3 months (adjusted relative risk 2.20; 95% CI 1.04-4.63, P = .038). CONCLUSION: The urinary C4d, serving as a non-invasive biomarker, is associated with the progression of IgAN and holds the potential to predict proteinuria response in this disease.

Treatment Location Variation for Chronic Limb-Threatening Ischemia in Patients With Kidney Failure.

INTRODUCTION: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions. METHODS: Chronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted. RESULTS: A total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention. CONCLUSIONS: Patients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race.

Safety and utility of panniculectomy in renal transplant candidates and end stage renal disease patients.

BACKGROUND: As the obesity crisis in the United States continues, some renal transplantation centers have liberalized their BMI criteria necessary for transplant eligibility. More individuals with larger body-habitus related comorbidities with End-Stage Renal Disease (ESRD) now qualify for renal transplantation (RT). Surgical modalities from other fields also interact with this patient population. METHODS: In order to assess surgical outcomes of panniculectomy in the context of renal transplantation and ESRD, the authors performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. Due to a paucity of existing primary studies, we retrospectively collected data on patients with ESRD undergoing panniculectomy from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) to evaluate outcomes of body contouring in this patient population. RESULTS: From the systematic review, a total of 783 ESRD patients underwent panniculectomy among the studies identified. Of these, 91 patients underwent panniculectomy simultaneously to RT while 692 had their pannus resected prior to kidney transplant. The most common complication was hematoma followed by wound dehiscence. From the NSQIP database, 24 868 patients met the inclusion criteria for analysis. In the setting of renal transplant status, patients with diabetes, hypertension requiring medication, and requiring dialysis were more likely to suffer postoperative complications (OR 1.31, 1.15, and 2.2, respectively). However, upon sub-analysis of specific types of complications, the only retained association was between diabetes and wound complication. CONCLUSION: Preliminary data show that panniculectomy in ESRD patients appears to be safe, though with a nominal increased risk for complications. Pannus resection does not appear to impact post-transplantation outcomes, including long-term allograft survival. Larger, higher powered, randomized studies are needed to confirm the safety, utility, and medical benefit of panniculectomy in the context of renal transplantation.

Simultaneous split liver/kidney transplantation: A national and single center experience report.

BACKGROUND: End-stage liver disease (ESLD) and end-stage renal disease (ESRD) are prevalent diseases for which the definitive treatment is transplantation. With limited organ supply, strategies to maximize organ availability has led to increasing rates of split liver transplantations for ESLD patients. Therefore, simultaneous split liver and kidney transplantations (SSLK) for patients with ESLD and ESRD could represent a treatment option for comorbid patients. However, current practice and outcomes after SSLK are unknown. METHODS: We aim to report national trends and our experience with patients undergoing SSLK. We performed a retrospective review of the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research file from January 2011-April 2022. Descriptive analysis of preoperative characteristics, postoperative outcomes and actuarial graft and patient survivals are reported. RESULTS: National review of the UNOS transplant registry from 2011-2021 of adult patients undergoing initial transplantation via SSLK demonstrates that this procedure remains uncommon, with only 76 such cases captured in that time. Nevertheless, survival rates at 1, 3, and 5 years remains robust, at 94%, 92%, and 90% for patients overall, 90%, 88%, 88%, for the liver graft, and 93%, 91%, 88% for the kidney graft, respectively. Review of a single center experience with three such patients from 2019-2021 has shown a safe, enduring transplant option with no graft complications seen. CONCLUSIONS: SSLK is both safe and a feasible option to optimize organ supply while allowing recipients to receive quality liver and kidney grafts and should be considered more often by transplant centers going forward.

Risk factors for renal dysfunction after isolated intestinal transplantation.

INTRODUCTION: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. METHODS: This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p < .1 in univariate analysis were considered for multivariable modeling. RESULTS: Thirty-three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (ß = -.77, p < .01) and stoma days (ß = -.06, p < .01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. CONCLUSIONS: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.

Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis.

INTRODUCTION: IgA nephropathy (IgAN) can cause end-stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT). METHODS: Retrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival. RESULTS: Compared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90, p < .010, 95% CI [1.169-3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665, p = .044, 95% CI [.447-.989]), graft failure (HR .758, p = .002, 95% CI [.633-.907]), and death (HR .619, p < .001, 95% CI [.490-.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs. CONCLUSION: In patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality.

The short-term effect of hemodialysis on the level of high-sensitive cardiac troponin T - A systematic review.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have an increased risk of cardiovascular disease, but interpreting cardiac troponin is difficult in this population. The effect of renal replacement therapy (RRT) is important to consider when interpreting serial cardiac troponin T (cTnT) results for patients with ESRD suspected of acute coronary syndrome (ACS). The aim of this systematic review is to answer how low-flux hemodialysis (LF-HD), high-flux hemodialysis (HF-HD), and hemodiafiltration (HDF) affect the blood concentration of high-sensitive cardiac troponin T (hs-cTnT). METHOD: Several databases were searched and identified records were evaluated independently by two of the authors. Pre- and postdialysis hs-cTnT concentrations together with other relevant data were extracted from the included studies. The quality (potential bias and applicability issues) were assessed for each of the included studies. RESULTS: The literature search identified 2,540 records and 15 studies were included. The relative pre- to postdialysis change of hs-cTnT varied from -41 to 29%. LF-HD increased the hs-cTnT concentration with relative changes between 2 and 17%. HDF decreased the concentration with relative changes from -41% to -9%. Both increases and decreases were seen for HF-HD (-16% to 12%). DISCUSSION/CONCLUSION: In this systematic review, we found LF-HD to increase the hs-cTnT concentration and HDF to decrease the concentration. Results for HF-HD and unspecified HD are more heterogeneous. Because of the differences between the included studies, a meta-analysis was not meaningful. This systematic review can help with the assessment of patients with ESRD suspected of ACS in relation to hemodialysis/HDF treatment.

Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

Improvement of Encapsulating Peritoneal Sclerosis After Medical Treatment and Successful Deceased Donor Kidney Transplant in a Child: A Case Report.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an uncommon complication of long-term peritoneal dialysis (PD). Despite its rarity, EPS significantly increases morbidity and mortality in patients undergoing prolonged peritoneal dialysis. In children on PD, the incidence of EPS ranges from 0.5% to 7.3%. CASE: We present the case of a 13-year-old Omani boy diagnosed with end-stage kidney disease (ESKD) secondary to steroid-resistant nephrotic syndrome due to diffuse mesangial sclerosis at the age of 2 years. He was started on automated peritoneal dialysis (APD) on the same year and experienced four episodes of peritonitis, which were treated successfully with intraperitoneal (IP) antibiotics. In January 2023, he developed intermittent abdominal pain and chronic constipation, which progressed to daily vomiting, reduced oral intake, and weight loss. He later developed subacute intestinal obstruction which was managed conservatively. A CT scan of the abdomen revealed findings consistent with EPS. Following the diagnosis of EPS, peritoneal dialysis (PD) was discontinued, and the patient transitioned to hemodialysis. Treatment for EPS began with steroids and Tamoxifen. Subsequently, he underwent deceased donor kidney transplantation and was started on multiple immunosuppressive medications. During subsequent follow-up appointments, he was maintained on total parenteral nutrition (TPN) along with a soft diet. His overall condition improved significantly, enhancing his quality of life. CONCLUSION: This case highlights the risk of encapsulating peritoneal sclerosis (EPS) in patients undergoing long-term peritoneal dialysis. Transitioning to hemodialysis and kidney transplantation, combined with targeted treatments such as steroids and Tamoxifen, significantly improved the patient's condition and quality of life. Early diagnosis and intervention are crucial for effective management of EPS in children.

Water-soluble vitamins and trace elements in children with chronic kidney disease stage 5d.

Children receiving maintenance dialysis (chronic kidney disease (CKD) stage 5d) have unique risk factors for micronutrient deficiency or toxicity. Children receiving chronic dialysis often require specialized diet plans that may provide more than the recommended daily allowance (RDA) of water-soluble vitamins and micronutrients, with or without the addition of a kidney-friendly vitamin. The following is a comprehensive review of current literature on disorders of micronutrients in this population including those of water-soluble vitamins (vitamin C and vitamin B complexes) and trace elements (copper, selenium, and zinc) and has three areas of focus: (1) the risk factors and clinical presentations of disorders of micronutrients, both deficiency and toxicity, (2) the tools to evaluate micronutrient status, and (3) the central role of renal dietitians in optimizing nutritional status from a micronutrient perspective.