Isolated Kidney Transplantation Research Articles

Primary hyperoxaluria: Long-term outcomes of isolated kidney versus simultaneous liver/kidney transplant.

To compare long-term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH). The Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long-term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan-Meier plots and Cox proportional hazards models. We identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08-0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02-0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness. Patients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.

Primary hyperoxaluria in adults and children: a nationwide cohort highlights a persistent diagnostic delay.

Primary hyperoxalurias (PH) are extremely rare genetic disorders characterized by clinical heterogeneity. Delay in diagnosing these conditions can have detrimental effects on patient outcomes. The primary objective of this study is to assess the current diagnostic delay for PH. This nationwide, observational and retrospective study included patients who received a genetic diagnosis of PH types 1, 2 and 3 between 1 January 2015 and 31 December 2019. Diagnostic delay was defined as the duration between the onset of symptoms and the time of genetic diagnosis. A total of 52 patients (34 children and 18 adults) were included in the study, with 40 PH1 (77%), 3 PH2 (6%) and 9 PH3 (17%). At the time of diagnosis, 12 patients (23%) required dialysis. Among the PH1 patients, the predominant symptom at onset in adults was renal colic (79% of cases), whereas symptoms in children were more diverse (renal colic in 17% of cases). The diagnostic delay was significantly shorter in children compared with adults [median (interquartile range)]: 1.2 (0.1-3.0) versus 30 (17-36) years, respectively (P<.0001). RNA interference was utilized in 23 patients (58%). Five individuals (13%) underwent double liver-kidney transplantation, and five (13%) received isolated kidney transplantation, with lumasiran therapy in four patients. For PH2 and PH3 patients, the diagnostic delay ranges from 0 to 3 years, with renal colic as first symptom in 33% of cases. This extensive and recent cohort of PH underscores the considerable delay in diagnosing PH, particularly in adults, even in a country with a dedicated organization for enhancing the overall management of rare diseases. These findings reinforce the imperative for increased awareness among relevant specialties regarding the evaluation of urolithiasis.

Chronic kidney disease in patients with long-term type 1 diabetes mellitus

BACKGROUND: Patients with type 1 diabetes mellitus (T1D) have an earlier age of onset and a longer course of the disease, already by middle age they have the development of microand macrovascular diabetic complications that reduce the quality and duration of life.AIM: To evaluate the prevalence of chronic kidney disease (CKD) and other late complications of T1D depending on renal dysfunction in the population of patients with T1D with disease duration of 20 and more years, who underwent examination and treatment in Endocrinology Research Centre.MATERIALS AND METHODS: A one-stage single-center epidemiological non-randomised study was conducted using the database of Endocrinology Research Centre with the study of 500 patients’medical histories with long-term T1D (20 years and mores), without kidney damage and with CKD at different stages (CKD C1–C5, C5D, after transplantation), examined and treated from 2011 to 2023.RESULTS: Normal renal function was observed in 10.8% of patients (n=54). Terminal stage of CKD was reached in 28.0% (n=140), of which 12.4% were on renal replacement therapy with program hemodialysis (RRT-HD), and 12.0% after isolated kidney transplantation or combined kidney and pancreas transplantation, the rest were at different stages of CKD. Normoalbuminuria was observed in 15.4% (n=77) among 500 patients. The prevalence of late complications of DM among the examined patients was high and increasing with the progression of renal dysfunction: diabetic retinopathy was diagnosed in 96% of patients, distal symmetrical polyneuropathy — in 97% of patients, various forms of autonomic neuropathy — in more than half of patients. About 60% of patients had diagnosed arterial atherosclerosis in the legs, about one third — atherosclerosis of brachiocephalic arteries, 23% — confirmed coronary heart disease, and suffered cardiovascular events (myocardial infarction, acute cerebral circulation disorder) — 19% of patients, about half of whom had CKD of different severity. Factors for increased risk of cardiovascular disease: estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73m2, OR=7.1; 95% CI 3.6–8.4; p&lt;0.001), eGFR &lt;30 mL/min/1.73m2 OR=8.7; 95% CI 2.8–8.4; p&lt;0.001), eGFR &lt;15 mL/min/1.73m2 OR=14; 95% CI 6.3–31.3; p&lt;0.001); albuminuria &gt; 30 mg/g OR=2.4; 95% CI 1.6–3.6; p&lt;0.001), dialysis OR=14.1; 95% CI 6.2–32.1; p&lt;0.001), kidney transplant OR=11.7; 95% CI 5.4–24.9; p&lt;0.001). Manifestation of T1D between 1996–2002 reduced the risk of developing CKD by 10.75; 95% CI 4.37; 27.03) vs manifestation of T1D earlier. Age of T1D debut 6–17 years increased the risk of reaching terminal CKD vs age of debut &gt;18 years: OR=2.4; 95% CI 1.22; 5.022; p=0.012).CONCLUSION: Despite a significant reduction in the risk of developing CKD in individuals with T1D debut between 1996 and 2002, renal dysfunction is a frequent complication in patients with a long disease course, combining with other late complications and contributing to a high risk of terminal stage of CKD and cardiovascular events. Early age of T1D debut increases the risk of terminal CKD.

Post-transplant diabetes mellitus: Findings in nutritional status and body composition

IntroductionWeight gain and changes in body composition are associated with the onset of diabetes after kidney transplantation, and detailing these changes can help prevent this situation. The study aimed to assess the prevalence of diabetes mellitus after kidney transplantation and changes in the nutritional status and body composition in patients with diabetes one year from surgery. Materials and methodsThis survey was a single-center, prospective cohort study. Twenty-nine patients over 18 years old who underwent isolated kidney transplantation, without diabetes, were included and followed up for one year. At hospital discharge after transplantation and one year later, anthropometric (weight, height and abdominal circumference), body composition (electrical bioimpedance), routine biochemical and dietary intake assessments were performed. ResultsMost of the patients were male (75%), and the mean age was 48.0±11.8 years old. In the first-year post-surgery 27.6% of patients had DM and the diagnosis was made, on average, 4 months after transplantation. The group with diabetes had, from the beginning to the end of the study, greater weight and body fat, especially abdominal fat. The non-diabetic group, after one year, showed an increase in phase angle, body weight and body masses, more pronounced of fat-free mass, when compared with fat mass gain. ConclusionsBoth groups showed weight gain, but in the non-diabetic group these changes can be interpreted as an improvement in the nutritional profile. Metabolic abnormalities associated with immunosuppression and eating habits, combination that maintains increased the risk for diabetes for long time, keeping this group with priority in nutritional care.

Post-transplant diabetes mellitus: Findings in nutritional status and body composition

IntroductionWeight gain and changes in body composition are associated with the onset of diabetes after kidney transplantation, and detailing these changes can help prevent this situation. The study aimed to assess the prevalence of diabetes mellitus after kidney transplantation and changes in the nutritional status and body composition in patients with diabetes one year from surgery. Materials and methodsThis survey was a single-center, prospective cohort study. Twenty-nine patients over 18 years old who underwent isolated kidney transplantation, without diabetes, were included and followed up for one year. At hospital discharge after transplantation and one year later, anthropometric (weight, height and abdominal circumference), body composition (electrical bioimpedance), routine biochemical and dietary intake assessments were performed. ResultsMost of the patients were male (75%), and the mean age was 48.0±11.8 years old. In the first-year post-surgery 27.6% of patients had DM and the diagnosis was made, on average, 4 months after transplantation. The group with diabetes had, from the beginning to the end of the study, greater weight and body fat, especially abdominal fat. The non-diabetic group, after one year, showed an increase in phase angle, body weight and body masses, more pronounced of fat-free mass, when compared with fat mass gain. ConclusionsBoth groups showed weight gain, but in the non-diabetic group these changes can be interpreted as an improvement in the nutritional profile. Metabolic abnormalities associated with immunosuppression and eating habits, combination that maintains increased the risk for diabetes for long time, keeping this group with priority in nutritional care.

Heart Failure Recovery After Lumasiran and Isolated Kidney Transplantation in Primary Hyperoxaluria Type 1

Heart Failure Recovery After Lumasiran and Isolated Kidney Transplantation in Primary Hyperoxaluria Type 1

Algorithm for Safe Hospital Discharge of Patients Submitted to Kidney Transplantation

Objective: To develop and validate an algorithm for safe hospital discharge after kidney transplantation (ASDKTx).Methods:This is a methodological study of algorithm development based on the following steps: 1) literature review; 2) historical cohort study, carried out in a reference transplant hospital in the city of Fortaleza - Ceará, including all isolated kidney transplant recipients, adults and children, that occurred between June 2017 and June 2019, who were discharged from the hospital for outpatient follow-up (n=265); 3) construction of the algorithm from the scientific evidence obtained in the literature review and information from the cohort study; 4) validation of the algorithm by expert judges, with the evaluation of the instruments in the domains: Objectives, Structure and Presentation and Relevance. Results: The sociodemographic profile of the patients in this study converges with the national literature. The overall mean length of hospital stay (HS) was 11 days, seven for living donor recipients and 11 for those who received a deceased donor transplant. The main early complications were: infection (25.6%), delayed graft function (31.6%), and surgical complications (8.3%), seven (2.7%) patients had rejection. All complications were associated with HS prolongation. The ASDKTx was validated by 19 expert judges in kidney transplantation, who considered the instrument adequate to support professionals in making decisions about patient discharge. All items of the evaluated dimensions presented an excellent Content Validity Index (CVI) equal to 1.00. Thus, the CVI of each domain was equal to 1.00, with a total CVI = 1.00. In the binomial analysis, the items presented p = 0.135, indicating no disagreement between the judges in the assigned score. The comments and suggestions supported the changes in the instrument that made it possible to define the final version of the algorithm. Conclusion: Given the common context of prolonged HS, an algorithm for safe discharge can be an essential strategy to improve understanding of the post-transplant care line and assess each patient for an early and safe discharge.

Inadvertent stem cell transfer demonstrating a way for tolerance induction

In this issue, Sobrino etal. present a case of hematopoietic chimerism and subsequent tolerance after isolated kidney transplantation in a pediatric patient with syndromic combined immune deficiency. This report not only highlights the chimerism approach for tolerance induction in transplantation, but it is also the first evidence of hematopoietic stem cells in human kidneys. This commentary discusses the potency and risks of the chimerism approach for tolerance induction after solid organ transplantation, especially in (pediatric) patients with immune deficiencies.

Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP

BackgroundNephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes.MethodsThe records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing.ResultsTwenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid.ConclusionsNPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival.

BACKGROUNDThe lack of space, as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms, remains controversial.AIMTo evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease. METHODSOne hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without (kidney transplant alone (KTA) group) and 77 with associated ipsilateral nephrectomy (KTIN group), were retrospectively reviewed. Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival. RESULTSCreation of space for future graft positioning was the main reason (n = 74, 96.1%) for associated ipsilateral nephrectomy. No significant difference in surgical comorbidity (lymphocele, wound infection, incisional hernia, wound hematoma, urinary infection, need for blood transfusion, hospitalization stay, Dindo Clavien classification and readmission rate) was observed between the two study groups. The incidence of primary nonfunction and delayed graft function was comparable in both groups [0% and 2.6% (P = 0.497) and 9.1% and 16.9% (P = 0.230), respectively, in the KTA and KTIN group]. The 1- and 5-year graft survival were 94.8% and 90.3%, and 100% and 93.8%, respectively, in the KTA and KTIN group (P = 0.774). The 1- and 5-year patient survival were 96.1% and 92.9%, and 100% and 100%, respectively, in the KTA and KTIN group (P = 0.168). CONCLUSIONSimultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short- and long-term graft survival.

Treatment of primary hyperoxaluria type 1.

ABSTRACTSupportive treatment for primary hyperoxaluria type 1 (PH1) focuses on high fluid intake and crystallization inhibitors. A subset of patients with specific PH1 genotypes (c.508G>A and c.454T>A) will respond to pyridoxine, defined as a >30% reduction in urinary oxalate excretion. Response to pyridoxine is variable and in some patients, urinary oxalate may normalize. The first focused treatment for PH1 using an RNA interference agent to reduce urinary oxalate was approved in 2020, and such therapies may significantly alter treatment approaches and long-term outcomes in PH1. Currently PH1 often presents with kidney function impairment and frequently results in end-stage kidney disease (ESKD). With kidney dysfunction, urinary oxalate clearance decreases and multisystem deposition of oxalate (oxalosis) occurs, commonly in bones, eyes, heart and skin. Once plasma oxalate levels exceed 30 µmol/L, aggressive haemodialysis is indicated to prevent oxalosis, even if the glomerular filtration rate (GFR) remains better than for typical dialysis initiation. Peritoneal dialysis alone does not achieve the needed oxalate clearance. Dialysis is a bridge to future transplantation. Liver transplantation restores hepatic alanine-glyoxylate transaminase enzyme activity, allowing glyoxylate detoxification and preventing further oxalosis. The native liver must be removed as part of this process to avoid ongoing pathologic oxalate production. The timing and type of liver transplantation are dependent on pyridoxine sensitivity, age, weight, residual GFR and evidence of systemic oxalate deposition in extrarenal organs. Liver transplant can be isolated or combined with kidney transplantation in a sequential or simultaneous fashion. Isolated kidney transplantation is generally reserved for pyridoxine-sensitive patients only. Although liver transplantation is curative for PH1 and kidney transplantation treats ESKD, ensuing necessary immunosuppression and potential allograft dysfunction impart significant long-term risks.

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

IntroductionIn primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver–kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes.MethodsWe used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed.ResultsA total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes.ConclusionThe CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.

Transplantation outcomes in patients with primary hyperoxaluria: a systematic review

BackgroundPrimary hyperoxaluria type 1 (PH1) is characterized by hepatic overproduction of oxalate and often results in kidney failure. Liver-kidney transplantation is recommended, either combined (CLKT) or sequentially performed (SLKT). The merits of SLKT and the place of an isolated kidney transplant (KT) in selected patients are unsettled. We systematically reviewed the literature focusing on patient and graft survival rates in relation to the chosen transplant strategy.MethodsWe searched MEDLINE and Embase using a broad search string, consisting of the terms ‘transplantation’ and ‘hyperoxaluria’. Studies reporting on at least four transplanted patients were selected for quality assessment and data extraction.ResultsWe found 51 observational studies from 1975 to 2020, covering 756 CLKT, 405 KT and 89 SLKT, and 51 pre-emptive liver transplantations (PLT). Meta-analysis was impossible due to reported survival probabilities with varying follow-up. Two individual high-quality studies showed an evident kidney graft survival advantage for CLKT versus KT (87% vs. 14% at 15 years, p<0.05) with adjusted HR for graft failure of 0.14 (95% confidence interval: 0.05–0.41), while patient survival was similar. Three other high-quality studies reported 5-year kidney graft survival rates of 48–89% for CLKT and 14–45% for KT. PLT and SLKT yielded 1-year patient and graft survival rates up to 100% in small cohorts.ConclusionsOur study suggests that CLKT leads to superior kidney graft survival compared to KT. However, evidence for merits of SLKT or for KT in pyridoxine-responsive patients was scarce, which warrants further studies, ideally using data from a large international registry.

Definition and Analysis of Textbook Outcome: A Novel Quality Measure in Kidney Transplantation.

"Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution. Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included. TO was defined by clinician consensus at our institution to include freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay > 75th percentile of kidney transplant patients, 90-day mortality, 30-day acute rejection, delayed graft function, and discharge with a Foley catheter. Recipient, operative, financial characteristics, and post-transplant patient, graft, and rejection-free survival were compared between patients who achieved and failed to achieve TO. A total of 557 kidney transplant patients were included. Of those, 245 (44%) achieved TO. The most common reasons for TO failure were delayed graft function (N = 157, 50%) and hospital readmission within 30days (N = 155, 50%); the least common was mortality within 90days (N = 6, 2%). Patient, graft, and rejection-free survival were significantly improved among patients who achieved TO. On average, patients who achieved TO incurred approximately $50,000 less in total inpatient charges compared to those who failed TO. TO in kidney transplantation was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer transplant centers a detailed performance breakdown to identify aspects of perioperative care in need of process improvement.

Immediate post-operative complications (I): Post-operative bleeding; vascular origin: Thrombosis pancreatitis.

Simultaneous pancreas-kidney transplantation is the treatment of choice for insulin-dependent diabetes that associates end-stage diabetic nephropathy, since it achieves not only a clear improvement in the quality of life, but also provides a long-term survival advantage over isolated kidney transplant. However, pancreas transplantation still has the highest rate of surgical complications among organ transplants. More than 70% of early graft losses are attributed to technical failures, that is, to a non-immunological cause. The so-called technical failures include graft thrombosis, bleeding, infection, pancreatitis, anastomotic leak and pancreatic fistula. Pancreatic graft thrombosis leads these technical complications as the most frequent cause of early graft loss. Currently most recipients receive postoperative anticoagulation with the aim of reducing the rate of thrombosis. Hemoperitoneum in the early postoperative period is a frequent cause of relaparotomy, but it is not usually associated with graft loss. The incidence of hemoperitoneum is clearly related to the use of anticoagulation in the postoperative period. Post-transplant pancreatitis is another cause of early postoperative complications, less frequent than the previous. In this review, we analyze the most common surgical complications that determine pancreatic graft losses.

Still diagnosed too late and under-recognized? The first comprehensive report on primary hyperoxaluria in Poland.

Primary hyperoxalurias (PHs) are rare disorders leading to overproduction and increased urinary excretion of oxalate. Three monogenic forms (PH1-PH3) were classified. PHs lead to urolithiasis and chronic kidney disease. There are only sparse data on patients with PH from Eastern European countries including Poland. The aim of the study was to evaluate the prevalence, genetic background, and clinical course of PH in the Polish population. This was a retrospective multicenter study including data of all identified and genetically confirmed Polish patients with PH. Between 1998 and 2019, 21 patients with PH were identified, including 13 patients with PH1 (62%), 2 with PH2 (9%), and 6 with PH3 (29%). In those with PH1, the most common mutation was c.508G>A in AGXT and in PH3, c.700+5G>T in HOGA1. Nine patients (69%) developed end‑stage renal disease at a median age of 13 years and 2 died. In 6 (46%) PH1 cases, the diagnosis was made only after patients had progressed to end‑stage renal disease and received isolated kidney transplantation, followed by graft failure. Combined liver‑kidney transplantation was performed in 6 patients with PH1. Two siblings with PH2 showed a milder course with slightly decreased renal function in one, at age of 11 years. Despite infantile onset of urolithiasis, all patients with PH3 at a median age of 10 years maintained normal renal function. The prevalence of PH1 and PH2 in Poland seems to be much lower than in Western countries with PH3 constituting about 30% of all cases. The molecular findings and clinical course are typical, but the underdiagnosis is of concern.

P0171NON COMPLIANCE AND ACUTE DEHYDRATION ARE MAIN REASON FOR ACUTE KIDNEY FAILURE IN NON-INFANTILE PRIMARY HYPEROXALURIA TYPE I (PH I)

Abstract Background and Aims Patients with primary hyperoxaluria type 1 have an increased risk of acute or chronic kidney failure (AKF/CKF). There are two risk groups: first the infantile oxalosis patients with an unremarkable family history and second, the adult patients with only an oligosymptomatic course (minor stone events), who get into end-stage renal disease (ESRD) due to oxalate-induced chronic inflammatory processes in the kidney. We were interested in the prevalence of acute kidney failure in the PH1 patients seen in our Hyperoxaluria Center over the last 10 years. Method We retrospectively analyzed the database of the German Hyperoxaluria Center for those patients being routinely seen in our outpatient clinic for AKF and its specific reason. AKF was defined as patients with a sudden onset of kidney failure and the necessity of dialysis installment, but a documented stable kidney function (no worse than stage 2-3 CKD) prior to onset of AKF. Results Currently, we routinely follow (3-4 times a year) 49 of 117 patients with genetically proven PH1. For the patients not routinely seen, we act as the reference center and primary lab. Out of the 117 PH1 patients, 6 had infantile oxalosis and thus early ESRD; 8 patients are currently on dialysis; and 6 patients have died, 2 patients each either post liver or liver/kidney transplantation (LTx, LKTx), under dialysis or as sudden death, the latter two due to systemic oxalosis. Transplantations were performed in 35 patients with PH1 (LKTx in 28 patients, LTx in 4 patients and 3 had an isolated kidney transplantation). Out of the 49 PH1 patients we routinely follow, AKF was diagnosed in 8 patients aged 11-56 years (one pediatric patient, 3 patients 18-19 years old, and 4 patients 29-56 years old), which has led to CKF and hence, maintenance hemodialyis in 7/8 and even death in one patient. Non-compliance regarding either medication or recommended fluid intake was the reason for AKF in 6 of the 8 patients, the 11 year-old girl, 2 adult patients and the 3 young adults being on the edge of leaving pediatric care. Acute massive diarrhea without adequate fluid substitution led to AKF in 2 middle aged male patients. Conclusion AKF is not uncommon in patients with PH1 and is frequently related to either non-compliance or to situations of severe fluid losses with inadequate fluid substitution. In the situations described, AKF is not based on already extremely altered renal function. Therefore, interruption of medication or lack of fluid intake, even for short periods of time, can lead to severe clinical consequences in these patients.

Impact de la pandémie de COVID-19 sur l’activité chirurgicale au sein des services d’urologie de l’Assistance Publique – Hôpitaux de Paris

RésuméIntroductionEn conséquence de la pandémie de COVID-19 en France, toute activité chirurgicale non urgente a dû être annulée à partir du 12 mars 2020. Afin d’anticiper la reprise des interventions décalées, une quantification de la réduction d’activité est nécessaire. L’objectif de l’étude était d’évaluer comparativement à 2019 la réduction d’activité chirurgicale urologique adulte pendant la pandémie de COVID-19.Matériel et méthodesNous avons comparé le nombre d’interventions urologiques pratiquées dans les 8 services universitaires d’urologie de l’Assistance Publique – Hôpitaux de Paris (AP–HP) sur deux périodes comparables (14–29 mars 2019 et 12–27 mars 2020) à l’aide du logiciel de planification opératoire et du PMSI partagé par ces centres. L’intitulé d’intervention et le type de chirurgie ont été collectés et regroupées en 16 catégories.RésultatsUne baisse de l’activité globale à l’AP–HP en urologie de 55 % entre 2019 et 2020 (995 et 444 interventions respectivement) a été constatée sur les 8 services. L’activité oncologique et les urgences ont diminué de 31 % et 44 %. L’activité de transplantation rénale, la chirurgie fonctionnelle et andrologique ont subi les plus fortes baisses d’activité par les interventions non oncologiques (−92 %, −85 % et −81 %, respectivement). Environ 1033 heures d’intervention devront être reprogrammées pour rattraper le programme opératoire annulé.ConclusionLe confinement et le report des interventions chirurgicales « non urgentes » ont entraîné une diminution drastique de l’activité chirurgicale au sein de l’AP–HP. Pendant cette période, les urologues ont été sollicités pour d’autres tâches mais doivent désormais s’atteler à organiser la période de reprise d’activité pour éviter une crise organisationnelle en urologique.Niveau de preuve3.

Donor-targeted serotherapy as a rescue therapy for steroid-resistant acute GVHD after HLA-mismatched kidney transplantation.

Acute graft-versus-host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor-targeted therapy would ideally mitigate graft-versus-host reactivity while sparing recipient immune functions. We report two children with end-stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid-resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti-HLA donor-specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti-HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA-rich plasma was well tolerated and notably did not induce antibody-mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation-associated GVHD.

Individualized concept for the treatment of autosomal recessive polycystic kidney disease with end-stage renal disease.

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73m2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation.