Autosomal Dominant Polycystic Disease Research Articles

A clinical case of surgical treatment of a large kidney cyst in a 9-year-old girl with autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease is currently the most common inherited form of cystic kidney disease, the frequency of which is about 1 per 400–1000 newborns, what makes the problem relevant. Its progressive course in patients with polycystic disease is primarily associated with the ischemic component, the severity of which depends on the number, location and size of cysts. Arterial hypertension, which is an autosomal dominant polycystic kidney disease complication, plays a leading role in renal failure progression. Given the current lack of specific treatment, the main therapeutic goal is to prevent complications, postpone the development of renal failure. Therefore, if there are large and giant cysts, surgical treatment is an effective modality and should be performed in a timely manner.
 CLINICAL CASE DESCRIPTION: The authors present a clinical case of a successful endovideosurgical cyst excision in a -year-old patient with a giant cyst in the right kidney, autosomal dominant polycystic disease, and hypertension of renal genesis.
 Endovideosurgical cystectomy in the patient with autosomal dominant polycystic kidney disease has become an important pathogenetic link in the treatment of this pathology. Currently, the patient is under dynamic follow-up for more than one year. During the follow-up period, the patient demonstrates relief of urinary syndrome in the form of disappeared haematuria, stabilization of albuminuria indices, improvement of blood flow parameters in the renal parenchyma, as well as stabilization of arterial pressure.
 CONCLUSION: The given clinical example demonstrates that reasonable surgical intervention with the choice of a rational method of access, taking into account the anatomical localization and size of the cystic formation, allowed to obtain a good result in the form of stabilization of renal hemodynamics in a patient with autosomal dominant polycystic kidney disease.

Calculation of Kidney Volumes with Magnetic Resonance in Patients with Autosomal Dominant Polycystic Kidney Disease: Comparison between Methods

Autosomal dominant polycystic renal disease (ADPKD) is the most frequent kidney inheritable disease, characterized by the presence of numerous bilateral renal cysts, causing a progressive increase in total kidney volume (TKV) and a progressive loss of renal function. Several methods can be used to measure TKV by using MRI, and they differ in complexity, accuracy and time consumption. This study was performed to assess the performance of the ellipsoid method and the semi-automatic segmentation method, both for TKV and SKV (single kidney volume) computation. In total, 40 patients were enrolled, and 78 polycystic kidneys analyzed. Two independent operators with different levels of experience evaluated renal volumetry using both methods. Mean error for ellipsoid method for SKV computation was −2.74 ± 11.79% and 3.25 ± 10.02% for the expert and the beginner operator, respectively (p = 0.0008). A Wilcoxon test showed a statistically significant difference between the two operators for both methods (SKV p = 0.0371 and 0.0034; TKV p = 0.0416 and 0.0171 for the expert and the beginner operator, respectively). No inter-operator significant difference was found for the semi-automatic method, in contrast to the ellipsoid method. Both with a Wilcoxon test and Bland–Altman plot, statistically significant differences were found when comparing SKV and TKV measurements obtained with the two methods for both operators, even if the differences are stronger for the beginner operator than for the expert one. The semi-automatic segmentation method showed more inter-observer reproducibility. The ellipsoid method, in contrast, appears to be affected by greater inter-observer variability, especially when performed by operators with limited experience.

Fetal renal cystic disease and post-natal follow up-a single center experience.

Prenatal sonographic evidence of large, echogenic, or cystic kidneys may indicate any one of a diverse set of disorders including renal ciliopathies, congenital anomalies of the kidney and urinary tract (CAKUT), or multisystem syndromic disorders. Systematic transition planning for these infants from in utero detection to post-natal nephrology management remains to be established. We sought to evaluate the presentation and transition planning for infants identified in utero with bilateral renal cystic disease. Our retrospective observational study identified 72 pregnancies with bilateral renal cystic disease in a single center from 2012 to 2022; 13 of which had a confirmed renal ciliopathy disorder. Clinical and imaging data, genetic test results, and documentation of postnatal follow-up were collected and compared. In our suspected renal ciliopathy cohort (n = 17), autosomal recessive polycystic disease (ARPKD) was the most common diagnosis (n = 4), followed by Bardet-Biedl syndrome (BBS, n = 3), autosomal dominant polycystic disease (ADPKD, n = 2), HNF1B-related disease (n = 2), and Meckel-Gruber syndrome (MKS, n = 2). Four cases were not genetically resolved. Anhydramnios was observed primarily in fetuses with ARPKD (n = 3). Polydactyly (n = 3) was detected only in patients with BBS and MKS, cardiac defects (n = 6) were identified in fetuses with ARPKD (n = 3), MKS (n = 2), and BBS (n = 1), and abnormalities of the CNS (n = 5) were observed in patients with ARPKD (n = 1), MKS (n = 2), and BBS (n = 3). In general, documentation of transition planning was incomplete, with post-natal nephrology management plans established primarily for infants with renal ciliopathies (n = 11/13; 85%). Prenatal sonographic detection of echogenic kidneys should raise suspicion for a broad range of disorders, including renal ciliopathies and CAKUT. Multicenter collaboration will be required to standardize the implementation of transition guidelines for comprehensive nephrology management of infants identified in utero with enlarged, echogenic kidneys.

Consensus document on autosomal dominant polycystic kindey disease from the Spanish Working Group on Inherited Kindey Diseases. Review 2020

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent cause of genetic renal disease and accounts for 6–10% of patients on kidney replacement therapy (KRT).Very few prospective, randomized trials or clinical studies address the diagnosis and management of this relatively frequent disorder. No clinical guidelines are available to date. This is a revised consensus statement from the previous 2014 version, presenting the recommendations of the Spanish Working Group on Inherited Kidney Diseases, which were agreed to following a literature search and discussions. Levels of evidence mostly are C and D according to the Centre for Evidence-Based Medicine (University of Oxford). The recommendations relate to, among other topics, the use of imaging and genetic diagnosis, management of hypertension, pain, cyst infections and bleeding, extra-renal involvement including polycystic liver disease and cranial aneurysms, management of chronic kidney disease (CKD) and KRT and management of children with ADPKD. Recommendations on specific ADPKD therapies are provided as well as the recommendation to assess rapid progression.

MO012: Development of an Accurate Automated Segmentation Algorithm to Measure Total Kidney Volume in ADPKD Suitable for Clinical Application (The Cystvas Study)

Abstract BACKGROUND AND AIMS A major barrier to the routine adoption of total kidney volume (TKV) as a clinical biomarker of disease for autosomal dominant polycystic disease (ADPKD) is the significant human operator time required even by experienced analysts (typically, 45–90 min per patient). Several groups have investigated automated and semi-automated kidney segmentation methods to either reduce or eliminate the human interaction required. However, such tools have mostly been developed using data from single centers, which may not translate well to other centers. To date, there has been little attempt to develop or validate algorithms using multi-center and multi-scanner data. Here, we report an automated segmentation tool capable of high performance across different patient populations and scanner sequences using 1.5 T MRI data from four centers (the CYSTic consortium). The algorithm was subsequently tested in a separate clinical cohort to assess its likely performance during routine clinical use. METHOD All 1.5 T studies from the CYSTic trial were downloaded (acquired from Siemens Avanto, GE Optima and Siemens Aera, using different sequences). Cases with poor image quality or with sections of kidney missing from the field of view were excluded. A single, experienced operator selected the most appropriate image series for segmentation and manually segmented each patient's kidneys using a commercial software program (MIM Encore). There were 454 kidneys segmented from 227 scans. These data were used for algorithm training and validation. In addition, 48 routine clinical scans from the Sheffield 3D Lab were extracted from the archives along with their original segmentations (performed by six different analysts), to use as a test set. None of the patients in the clinical test set were included in the training set. An ensemble U-net algorithm was created using the nnUNet approach Isensee et al. (nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation. Nat Meth 2021; 18(2): 203–211), whereby the CYSTic data were used in a 5-fold cross-validation, with stratification across the four centers (i.e. each center contributed 80% of the available data to algorithm training in each fold). Algorithm training proceeded according to the standard heuristic nnUnet functions, using a 3D architecture, for 100 epochs. Segmented kidneys were split into left and right sides during post-processing, through analysis of the position of the center of gravity of segmented regions. Once trained, the five algorithms from cross-validation were applied in an ensemble to the clinical test cohort. RESULTS In both cross-validation and clinical testing phases, the median DICE score was 0.96 for each kidney (IQR of 0.95–0.97 in cross-validation on both sides, And 0.95–0.97 on the left side for clinical testing and 0.96 for the right). The median total kidney volume error was −0.46% (−2.02 to 1.27) for the left side in cross-validation and −0.82% (−2.55 to 0.86) for the right. In the clinical testing phase, the median volume errors were −1.8% (−3.69 to 1.29), left and −1.79% (−3.95 to 0.65), right. The mean time taken to manually segment kidneys in the CYSTIc dataset was 54 min per scan (SD of 31 min). Use of the algorithm as a first pass segmentation, with subsequent checking and editing by an operator, would significantly reduce human input time to a few minutes per case CONCLUSION Our new algorithm demonstrates high accuracy compared to the gold standard of manual TKV segmentation and performs well in a wide range of patients with ADPKD imaged using different scanners at several European centers. Its high performance in a real-world clinical dataset demonstrates that such tools can provide a reliable means of measuring TKV in routine practice and reduces the previous barrier of analyst time and experience.

A Case Report of COVID-19 in a Living Kidney Transplant Recipient: A Challenging Case with Complete Rehabilitation

Adjustment of immunosuppressive and COVID-19 treatment in terms of drug interactions is still challenging. Herein, we report a 45-year-old woman with end-stage renal disease due to autosomal dominant polycystic diseases (ADPKD) with COVID-19 and pulmonary involvement following kidney transplantation. The patient was properly treated by discontinuation of immunosuppressive drugs, bronchoscopy, and high volume of blood transfusions. The fact that we quickly used early intubation and a new treatment regimen that suppressed immune systems may help physicians develop optimal treatment strategies for similar severe cases. However, this treatment method requires more detailed evaluations due to the contradictory results in reviewing other studies.

Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach.

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment.

PKD1 Compared With PKD2 Genotype and Cardiac Hospitalizations in the Halt Progression of Polycystic Kidney Disease Studies

Autosomal dominant polycystic disease (ADPKD) is a genetic disorder characterized by progressive development and enlargement of kidney cysts that ultimately lead to loss of kidney function in most individuals.1 ADPKD is primarily caused by mutations in the PKD1 and PKD2 genes.1 Although the hallmark of ADPKD is an increase in total kidney volume with progressive loss of kidney function owing to the accumulation of kidney cysts, cardiovascular complications are a leading cause of death.2 Notably, polycystin 1 and 2 are expressed in vascular endothelial and vascular smooth muscle cells.

Value of FDG-PET/CT in monitoring cyst infections in patients with autosomal dominant polycystic renal disease.

Value of FDG-PET/CT in monitoring cyst infections in patients with autosomal dominant polycystic renal disease.

Autosomal Dominant Polycystic Disease of the Kidneys as one of the Primary Diseases to the Patients on the Chronic Dialysis Program

With this notice I would like to remind all of us to an important topic such as Autosomal dominant polycystic kidney disease which...

Simultaneous bilateral laparoscopic nephrectomy with kidney transplantation in patients with ESRD due to ADPKD: A single-center experience.

Patients with autosomal dominant polycystic disease (ADPKD) may require bilateral nephrectomy (BN) in addition to kidney transplantation (KT) for symptom control. This study aims to compare simultaneous BNKT to contemporaneous controls by reviewing our cohort of ADPKD patients who underwent KT from a living donor from January 2014 to October 2019. Symptomatic patients who underwent laparoscopic BNKT were compared to KT alone. Clinical differences related to undertaking bilateral nephrectomies showed increased total kidney volumes (P<.001). We assessed operative parameters, complications, and clinical outcomes. The complications were classified according to the Clavien-Dindo system. In 148 transplant recipients, 51 underwent BNKT, and 97KT alone. There was no difference in baseline demographics. BNKT recipients had longer cold ischemia time, required more ICU care, increased blood transfusions and longer hospital stays. The kidney function was similar in the first year in both groups, with no difference in delayed graft function, readmissions or severe grade III and IV complications within 3months after surgery. Laparoscopic BNKT is safe and feasible at the time of living donor KT. Although higher acuity care is needed with a longer initial hospital stay, there are comparable posttransplant patient and allograft outcomes.

Importance of family segregation in the American College of Medical Genetics and Genomics and Association of Molecular Pathology guidelines: Case of a Korean family with autosomal dominant polycystic disease

Importance of family segregation in the American College of Medical Genetics and Genomics and Association of Molecular Pathology guidelines: Case of a Korean family with autosomal dominant polycystic disease

P1707SIMULTANEOUS HEART-KIDNEY TRANSPLANT: OUR 10 YEARS' EXPERIENCE

Abstract Background and Aims The number of patients listed and receiving simultaneous heart-kidney transplantation (SHKT) has significantly increased in the last decade. This is likely due to the increased knowledge that SHKT is associated with a significant survival benefit in patients with heart failure with chronic kidney disease (CKD), compared to isolated heart transplant and sequential heart and kidney transplantation. Recent analysis of large data bases has shown a survival benefit in SHKT even in older patients and beyond dialysis dependent patients. However, this benefit is only proven for irreversible CKD which is often difficult to prove in patients with severe heart failure. Our center has the largest experience in SHKT in Portugal, and our aim is to report our experience with a total of 8 recipients and their outcomes after 10 years of follow up. Method We performed a retrospective analysis of all the patients submitted to SHKT in Coimbra University Hospital Center from 1 January 2009 to 31 December 2019. Data was collected using the clinical and laboratorial registries from our database. Follow up at December 2019 varied between 6 months to 10 years (median 5,5 years). Results A total of 8 patients received SHKT between 1 January 2009 and 31 December 2019. Only one patient was female and the mean age at transplant was 58.88 ± 9.7 years. The etiology of heart failure was dilated cardiomyopathy (N=4, 50%), severe valvular disease (N=2, 25%), ischemic cardiomyopathy (N=1, 12,5%) and one patient had familiar amyloidosis (N=1, 12,5%). Regarding CKD, the majority of the patients had type 2 cardiorenal syndrome (N=5, 62,5%), one patient had calcineurin toxicity due to previous liver transplantation, one patient had autosomal dominant polycystic disease, and in one patient the etiology remained unknown. Half of the patients were on chronic hemodialysis program for more than 3 months, and the remaining were preemptive. Regarding post-transplant results, average hospitalization was 19 days. Seven patients (87,5%) had immediate cardiac graft function (mean LVEF 70 ± 5.8% and mean PSAP 22.25 ± 5.6 mmHg). One patient had acute cardiac and subsequent renal graft dysfunction and died during hospitalization. Regarding renal graft outcomes, besides the patient that died, another patient had primary renal graft dysfunction due to renal artery thrombosis and one patient presented late graft function. The remaining five patients had immediate graft function and presented normal kidney graft function at follow up. Regarding complications, neoplasia was reported in two patients (one with sarcoma and the other with prostatic cancer), and there were twenty-five episodes of infection, present in all patients. Mortality at follow up was 37% (N=3). One of these, described above, died during hospitalization twenty-two days after transplant, and the other two died 4 and 5 years later due to a cardiovascular event and sarcoma, respectively. At follow up in 2019 five patients present stable kidney graft, good cardiac function and no recent complications. Conclusion In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation might be the best approach and appears to be associated with better graft and patient survival. Despite having a small number of cases, our center has the biggest experience in SHKT in Portugal and our results are very satisfying. A multidisciplinary approach between Nephrology, Cardiology and Cardiothoracic Surgery is fundamental and in the next decades it is expected an increase in SHKT number.

Autosomal dominant polycystic kidney disease

Autosomal dominant polycystic disease represents the most commonly encountered nephrologic pathology among genetic kidney disease. It is characterized by the emergence and uncontrolled growth of renal cysts due to a mutation occurring in one of the PKD1 and PKD2 genes. Often this nephrological pathology is ac­com­panied by extrarenal manifestations, therefore these patients’ ma­nage­ment requires a complex approach from ne­phro­logist, cardiologist and general physician.

Embolisation artérielle des reins polykystiques en alternative à la néphrectomie ergonomique en pré greffe rénale. Étude monocentrique rétrospective sur 15 cas

This study aims at providing a retrospective assessment of the decrease in renal volume after renal artery embolization (RAE) among a group of patients with autosomal dominant polycystic renal disease and for whom transplantation, for ergonomic reasons was temporarily advised against. Between November 2014 and March 2017, as part of pre-transplantory procedure 15 patients, including 11 men and 4 women benfited from renal embolization (RAE) in a context of preparation for transplant in Lille University Hospital. All of the patients were suffering from autosomal dominant polycystic renal disease (ADPKD) at a severe or terminal stage of renal disease. The original mean total kidney volume (TKV) was 2550.6 cm3±1771 (1102 cm3; 7310 cm3), the average TKV at 3 months was 1684 cm3±1539 (648 cm3; 6930 cm3) with an average decrease of 33% in the volume (5.2%; 83.9%) (95% confidence interval [0.229-0.436]) (P<0.01) and 1632±1743 (599 cm3; 6758 cm3) at 6 months with an average decrease of 40.7% (7.6%; 64.1%) (IC95% 0.306-0.508) (P<0.01). Among the 15 patients, 13 had their contraindication removed and to date 7 have had successful transplants. One failure due to a very high initial volume (7310cm3) required a secondary nephrectomy. No post-embolization syndrome has been noticed, 2 minor complications occurred (13%) involving a difficult resumption of transit and there was one case of hematuria. ERA procedures must have a place in the ergonomic transplant strategy of patients with ADPKD with a low complication rate and a high efficiency. Nephrectomy indications before transplantation must therefore be reconsidered due to a major postoperative risk. Our results are in line with larger scale studies. Nevertheless, these results need to be confirmed by a large-scale randomized prospective study. 4.

Co-segregation of candidate polymorphism rs201204878 of the PKD1 gene in a large Iranian family with autosomal dominant polycystic disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of end-stage renal disease, occurring at a frequency of 1 in 400 to 1 in 800 individuals among different populations. The disease affects all ethnic groups worldwide, and there is a requirement for population-based studies to be conducted in order to improve diagnosis, genetic counseling and treatment. A large Iranian family with ADPKD was recruited for the current study. Clinical evaluation was performed to diagnose and assess disease progression in 11 members of this family, including 7 affected members and 4 unaffected members. PKD1 and PKD2 genes were genotyped in subjects by next-generation sequencing (NGS). Mutational analysis of PKD1 and PKD2 genes in this family revealed three intronic variations and three synonymous exonic variants in the PKD2 gene, and two non-synonymous exonic variants and eight intronic variants in PKD1, resulting in a total of 16 heterozygous variations among these two genes. Among the 16 variations, all except three intronic variants in the PKD1 gene have already reported in the Iranian population. The three novel mutations were predicted to be deleterious polymorphisms using in silico methods. Among the reported intronic variations, rs201204878 was identified as a splice region variant, leading to truncation of the polycystin-1 protein. In conclusion, genotyping of PKD1 and PKD2 in this family with ADPKD revealed no mutational hot spots. However, genetic screening identified three novel variants in the Iranian population. The data generated in the present study will contribute to improving the diagnosis, genetic counseling and treatment of patients with ADPKD.

What can copeptin tell us in patients with autosomal dominant polycystic disease?

Vasopressin is known to contribute to disease progression in autosomal dominant polycystic disease (ADPKD) by its influence on cyclic adenosine monophosphate that directly promotes cyst growth. In addition, vasopressin probably contributes to progression by inducing glomerular hyperfiltration as shown in other forms of chronic kidney diseases. The measurement of plasma copeptin, a marker of vasopressin secretion, could help identify patients at higher risk of fast progression and those expected to benefit the most from vasopressin V2 receptor blockade. Further studies should evaluate the optimal level of suppression of vasopressin effects in autosomal dominant polycystic disease.

Therapies for Childhood Polycystic Kidney Disease

Renal cysts are present in a wide variety of hereditary renal diseases in children. The term polycystic kidney disease (PKD) refers to two specific hereditary diseases, distinguished by the usual age of onset and genetic cause: autosomal recessive polycystic kidney disease/congenital hepatic fibrosis (ARPKD/CHF, MIM *606702) and autosomal dominant polycystic disease (ADPKD-OMIM *601313 and OMIM *173910). ARPKD/CHF is characterized by cystic dilations of the renal collecting ducts and developmental defects of biliary ductal plate remodeling, resulting in varying degrees of congenital hepatic fibrosis. ARPKD/CHF is commonly diagnosed in utero or at birth but can remain silent well into adolescence and rarely into adulthood. ADPKD, the most common inherited renal disease is characterized by slow, progressive enlargement of fluid-filled cysts leading to renal failure by the fifth to sixth decade of life in addition to various extrarenal manifestations. ADPKD can manifest in utero, infants, and children and can be a significant cause of morbidity and mortality in this age group. The genetic basis of ARPKD and ADPKD has largely been identified but continues to evolve. Despite remarkable advances in understanding the basic molecular and cellular pathophysiology, the development of targeted therapies has proven difficult. The complex structure of the genes and proteins, the tremendous allelic heterogeneity, complex inheritance patterns, and functional interactions of both the genes and proteins products of ARPKD and ADPKD complicate diagnostic and prognostic assessments. None the less, multiple therapeutic interventions are being tested in clinical trials, two clinical trials aimed at pediatric PKD patients are underway and one therapy, Tolvaptan, has been approved for adults use in Japan, Europe and recently in the USA. This review will discuss: 1) the clinical manifestations and genetics of childhood PKD; 2) how our understanding of the molecular and cellular pathophysiology of PKD is guiding current therapies; and 3) how recent discoveries may shape future therapies.

Serum Fas Ligand, Serum Myostatin and Urine TGF-β1 Are Elevated in Autosomal Dominant Polycystic Kidney Disease Patients with Impaired and Preserved Renal Function

Background/Aims: The pathophysiology of renal disease progression in autosomal dominant polycystic disease (ADPKD) is largely unknown. Recent evidence suggests microvascular dysfunction leading to renal ischemia, as an additional pathway for renal function decline. This study examined the levels of serum Fas ligand (FasL), serum myostatin and urine transforming growth factor-beta 1 (TGF-β1) and their association with markers of endothelial dysfunction, in ADPKD patients with preserved or impaired renal function. Methods: Seventy-eight participants were enrolled in the study, divided in three groups: Group A consisted of 26 ADPKD patients with impaired renal function (eGFR 45-70 ml/min/1.73m²), Group B of 26 ADPKD patients with preserved renal function (eGFR > 70 ml/min/1.73m²), and Group C of 26 age- and sex- matched controls with no history of renal disease. Serum FasL, myostatin and urine levels of TGF-β1 were measured as biomarkers of vascular dysfunction, apoptosis and fibrosis with ELISA techniques. Results: Group A patients had significantly higher levels of FasL (13.12±1.69 ng/mL), myostatin (4.62±0.59 ng/mL) and urine logTGF-β1 (3.56±0.49 ng/24h) compared to Group B (9.6±1.28 ng/mL, 3.06±0.35, and 2.09±0.37, respectively, p< 0.001 for all comparisons) or controls (6.59±1.17 ng/mL, 2.18±0.45 ng/ml, and 1.58±0.21, respectively, p< 0.001 for all comparisons). Patients in Group B had also higher levels of all markers compared to controls (p< 0.001), despite having similar renal function. In ADKPD patients negative associations of eGFR with FasL (r=-0.799, p< 0.001), myostatin (r=-0.856, p< 0.001) and TGF-β1 (r=-0.476, p< 0.001) but positive correlations of these markers with asymmetric dimethylarginine (ADMA) (r=0.825; r=0.749; and r=0.599, respectively p< 0.001) were noted. Multivariate analysis demonstrated that FasL was independently associated with high urine TGF-β1 (OR 3.774, 95%CI 1.180-12.072, p=0.025). Conclusions: ADPKD patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-β1 than controls. These results indicate that an interplay between endothelial dysfunction and renal ischemia with mechanisms linked to apoptosis and fibrosis may be present even in early stages of ADPKD.

Polycystic kidney disease: Tolvaptan slows disease progression in late-stage ADPKD.

New data from the REPRISE trial confirms that tolvaptan slows the progression of autosomal dominant polycystic disease (ADPKD). Although not yet approved by the United States Food and Drug administration, tolvaptan is now likely to become standard care for early and later stages of ADPKD in Europe and in various countries worldwide.