Simultaneous ipsilateral nephrectomy during kidney transplantation in autosomal dominant polycystic kidney disease: a matched pair analysis of 193 consecutive cases.

BACKGROUND: In end-stage renal transplant recipients with autosomal-dominant polycystic kidney disease (ADPKD), the imperative, optimal timing, and technique of native nephrectomy remains under discussion. The Freiburg Transplant Center routinely performs a simultaneous ipsilateral nephrectomy. METHODS: From April 1998 to May 2017, we retrospectively analyzed 193 consecutive ADPKD recipients, receiving per protocol simultaneous ipsilateral nephrectomy and compared morbidity, mortality, and outcome with 193 non-ADPKD recipients of a matched pair control. RESULTS: The incidence of surgical complications was similar with respect to severe medical, surgical, urological, vascular, and wound-related complications as well as reoperation rates and 30-day mortality. Intraoperative blood transfusions were required more often in the ADPKD (22.8%) compared with the control group (6.7%; p < 0.0001). Early postoperative urinary tract infections occurred more frequent (ADPKD 40.4%/control 29.0%; p = 0.0246). Time of surgery was prolonged by 30 min (ADPKD 169 min; 95%CI 159.8-175.6 min/control 139 min; 95%CI 131.4-145.0 min; p < 0.0001). One-year patient (ADPKD 96.4%/control 95.8%; p = 0.6537) and death-censored graft survival (ADPKD 94.8%/control 93.7%; p = 0.5479) were comparable between both groups. CONCLUSIONS: With respect to morbidity and mortality, per protocol, simultaneous native nephrectomy is a safe procedure. Especially in asymptomatic ADPKD KTx recipients, the number of total operations can be reduced and residual diuresis preserved up until transplantation. In living donation, even preemptive transplantation is possible.

Clinical burden of autosomal dominant polycystic kidney disease.

There are no specific therapies for autosomal dominant polycystic kidney disease (ADPKD), and clinical data evaluating the effects of non-specific therapies on ADPKD patients are scarce. We therefore evaluated those effects using data from a longitudinal health insurance database collected from 2000-2010. We individually selected patients with and without ADPKD from inpatient data files as well as from the catastrophic illness registry in Taiwan based on 1:5 frequency matching for sex, age, and index year. The hazard ratios (HR) of all-cause mortality, ischemic stroke, hemorrhagic stroke and end-stage renal disease (ESRD) in ADPKD inpatients were elevated as compared to the controls. Similarly, ADPKD patients from the catastrophic illness registry had an increased risk of hemorrhagic stroke and ESRD. Allopurinol users also had an increased risk of all-cause mortality. The HR for developing ESRD after medication exposure was 0.47-fold for statin and 1.93-fold for pentoxifylline. These results reveal that patients with ADPKD (either inpatient or from the catastrophic illness registry) are at elevated risk for hemorrhagic stroke and ESRD, and suggest that allopurinol and pentoxifylline should not be prescribed to ADPKD patients due to possible adverse effects.

Nocturnal Hemodialysis Compared with Conventional Dialysis for End-Stage Renal Disease Treatment in Polycystic Kidney Disease Patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage renal disease (ESRD). Little is known about outcomes after in-center nocturnal hemodialysis (NHD) treatment in ADPKD patients with ESRD. OBJECTIVES: This study aimed to evaluate the effects of in-center NHD compared with conventional hemodialysis (CHD) and peritoneal dialysis (PD) in ADPKD. METHODS: We used data of ADPKD adult patients with ESRD in the hospital database from 2000 to 2016. Propensity score matching, competing-risk regression, and Cox regression models were used for analysis. RESULTS: A total of 170 ADPKD patients were included. The median follow-up time was 5.5 years. In the overall multivariate-adjusted analysis, no significant difference of mortality risk was found in NHD vs. CHD (hazard ratio [HR] 1.33, 95% CI 0.26-6.73, p = 0.31) and PD (HR 1.06, 95% CI 0.14-7.71, p = 0.55), respectively. The overall survival rate also was not significantly different among the 3 groups (p = 0.88). Based on the propensity score, 26 patients on CHD and 26 patients on PD were successfully matched to 13 NHD patients. In the matched analysis, NHD was not associated with a lower risk of mortality compared with CHD (HR 2.14, 95% CI 0.33-14.00, p = 0.31) and PD (HR 0.68, 95% CI 0.52-8.94, p = 0.55). The result was similar when treating renal transplantation as a competing event. However, NHD was associated with a lower rate of complications (38.5 vs. 84.6%, p = 0.003) and a higher level of serum albumin (p < 0.001) compared with PD. CONCLUSIONS: NHD may not be a better choice in survival compared with conventional dialysis modalities for ADPKD patients in this pilot study. Patients in NHD have fewer complications than PD. Future studies with large sample sizes and longer follow-up are required.

Epidemiology of Autosomal Dominant Polycystic Kidney Disease in Olmsted County.

BACKGROUND AND OBJECTIVES: The prevalence of autosomal dominant polycystic kidney disease (ADPKD) remains controversial. Incidence rates in Olmsted County, Minnesota, during 1935-1980 were previously reported. The current work extends this study to 2016. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Rochester Epidemiology Project and radiology databases of Mayo Clinic and Olmsted Medical Center (healthcare providers for Olmsted County) were searched to identify all subjects meeting diagnostic criteria for definite, likely, and possible ADPKD. Annual incidence rates were calculated using incident cases during 1980-2016 as numerator and age- and sex-specific estimates of the population of Olmsted County as denominator. Point prevalence was calculated using prevalence cases as numerator and age- and sex-specific estimates of the population of Olmsted County on January 1, 2010 as denominator. Survival curves from the time of diagnosis were compared with expected survival of the Minnesota population. RESULTS: The age- and sex-adjusted annual incidence of definite and likely ADPKD diagnosis during 1980-2016 was 3.06 (95% CI, 2.52 to 3.60) per 100,000 person-years, which is 2.2 times higher than that previously reported for 1935-1980 (1.38 per 100,000 person-years). The point prevalence of definite or likely ADPKD on January 1, 2010 was 68 (95% CI, 53.90 to 82.13) per 100,000 population. Much higher incidence rates and point prevalence were obtained when possible ADPKD cases were included. Contrary to the previous Olmsted County study, patient survival in this study was not different from that in the general population. CONCLUSIONS: The point prevalence of definite and likely ADPKD observed in this study is higher than those reported in the literature, but lower than genetic prevalence based on estimates of disease expectancy or on analysis of large population-sequencing databases.

Unilateral nephrectomy versus renal arterial embolization and technique survival in peritoneal dialysis patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder associated with progressive enlargement of the kidneys and liver. ADPKD patients may require renal volume reduction, especially before renal transplantation. The standard treatment is unilateral nephrectomy. However, surgery incurs a risk of blood transfusion and alloimmunization. Furthermore, when patients are treated with peritoneal dialysis (PD), surgery is associated with an increased risk of temporary or definitive switch to haemodialysis (HD). Unilateral renal arterial embolization can be used as an alternative approach to nephrectomy. METHODS: We performed a multicentre retrospective study to compare the technique of survival of PD after transcatheter renal artery embolization with that of nephrectomy in an ADPKD population. We included ADPKD patients treated with PD submitted to renal volume reduction by either surgery or arterial embolization. Secondary objectives were to compare the frequency and duration of a temporary switch to HD in both groups and the impact of the procedure on PD adequacy parameters. RESULTS: More than 700 patient files from 12 centres were screened. Only 37 patients met the inclusion criteria (i.e. treated with PD at the time of renal volume reduction) and were included in the study (21 embolized and 16 nephrectomized). Permanent switch to HD was observed in 6 embolized patients (28.6%) versus 11 nephrectomized patients (68.8%) (P = 0.0001). Renal artery embolization was associated with better technique survival: subdistribution hazard ratio (SHR) 0.29 [95% confidence interval (CI) 0.12-0.75; P = 0.01]. By multivariate analysis, renal volume reduction by embolization and male gender were associated with a decreased risk of switching to HD. After embolization, a decrease in PD adequacy parameters was observed but no embolized patients required temporary HD; the duration of hospitalization was significantly lower [5 days [interquartile range (IQR) 4.0-6.0] in the embolization group versus 8.5 days (IQR 6.0-11.0) in the surgery group. CONCLUSIONS: Transcatheter renal artery embolization yields better technique survival of PD in ADPKD patients requiring renal volume reduction.

Native Nephrectomy in Patients With Autosomal Dominant Polycystic Kidney Disease Evaluated for Kidney Transplantation.

Native nephrectomy (NN) in patients with autosomal dominant polycystic kidney disease (ADPKD) is indicated in cases of recurrent urinary tract infections and hematuria, neoplastic degeneration, and encumbrance. Timing, indication, and surgical approach of NN depends on the symptoms or policy of the center. The aim of our study is to evaluate our experience. In our retrospective study, we included 130 patients with a diagnosis of ADPKD from 530 patients evaluated for renal transplantation from 2011 to 2017. We analyzed the etiologic indication, the timing, and the complications of NN. In our cohort, 53 patients underwent open NN, 85% pre-kidney transplantation (KT), 13% post-KT, and only 1 case simultaneous with KT. In the pre-KT group, indications included: major indication was encumbrance in the. In the post-KT group, the major indication was infection followed by encumbrance, which developed after KT. Complications were: 3 cases of bleeding (1 required relaparotomy, 2 evolved into hematoma and radiological derange); 1 iatrogenic iliac artery injury, which was contextually repaired, and 5 cases of incisional hernia. At 35 ± 7.2 months follow-up, patients' survival was 96%; 1 patient died at the induction of anesthesia and 1 patient from sepsis after double NN and removal of nonfunctional transplanted kidney. NN is not without complications and should be performed when clearly indicated. In our experience, we preferred to perform NN before KT.

Clinical study on autosomal dominant polycystic kidney disease among North Tunisians.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 µmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.

Different Effects of Iron Indices on Mortality in Patients With Autosomal Dominant Polycystic Kidney Disease After Long-Term Hemodialysis: A Nationwide Population-Based Study.

OBJECTIVE: Iron supplementation and erythropoietin stimulating agents (ESAs) are essential for maintaining hemoglobin levels in hemodialysis patients. However, patients with autosomal-dominant polycystic kidney disease (PKD) have higher endogenous erythropoietin levels, so their recommended iron indices for hemodialysis patients may differ. This study evaluated iron profiles, including ferritin levels and transferrin saturation (TSAT) to identify factors affecting mortality in patients on dialysis, and those associated with mortality in patients with and without PKD. DESIGN: This cohort study from the Taiwan Renal Registry Data System stratified mortality risk by the presence of PKD recorded as the underlying disease. SUBJECTS: We enrolled 1346 hemodialysis patients with PKD and 82,873 hemodialysis patients without PKD. MAIN OUTCOME MEASURE: The primary outcome was 3-year all-cause mortality. Predictors included time-averaged and baseline serum ferritin levels and TSAT. Multivariate Cox regression analysis adjusting for age, comorbidities, and relevant laboratory parameters was used to estimate the all-cause hazard ratios (HRs) for mortality. RESULTS: The mean ages of patients with and without PKD were 56.2±13.2 and 61.7±13.5 years and the median follow-up time was 37 (15-76) months. The adjusted mortality risks for time-averaged ferritin levels >800 ng/mL (HR=1.52; 95% confidence interval: 1.40-1.65) or TSAT levels >50% (HR=1.46; 95% confidence interval: 1.30-1.65) were significantly higher among patients without PKD than those for patients with normal iron indices. However, a U-shaped curve of mortality against ferritin/TSAT levels was not observed in patients with PKD. In the sensitivity test, there was no difference among PKD patients who underwent regular ESA therapy and those who did not. CONCLUSION: Iron indices have different effects on mortality among patients with and without PKD. Iron supplementation, recommended serum ferritin levels, or TSAT should be monitored in hemodialysis patients, especially those without PKD. Clinicians should consider treating anemia in hemodialysis patients individually, especially in PKD.

Outcomes of patients with autosomal-dominant polycystic kidney disease on peritoneal dialysis: A meta-analysis.

BACKGROUND: Complications related to peritoneal dialysis (PD) in patients with autosomal-dominant polycystic kidney disease (ADPKD), including intraperitoneal rupture of renal cyst, hernia, membrane failure and peritonitis, have been reported. However, long-term clinical outcomes of ADPKD patients on PD remain unclear. We performed this meta-analysis to assess the risks of death, technique failure and peritonitis in ADPKD patients on PD. METHODS: A systematic review was conducted using MEDLINE, EMBASE and Cochrane databases from inception to October 2017 to identify studies that evaluated the outcomes of ADPKD patients on PD, including the risks of death, technique failure and peritonitis. Non-ADPKD patients on PD were used as controls. Effect estimates from the individual study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Twelve cohort studies with a total of 14 673 patients on PD (931 ADPKD and 13 742 non-ADPKD patients) were enrolled. Compared with non-ADPKD status, ADPKD was associated with significantly decreased mortality risk with pooled odds ratio (OR) of 0.68 (95% confidence interval (CI), 0.53-0.86; I2 = 0). There were no associations of ADPKD with the risks of technique failure of PD and peritonitis with pooled OR of 0.93 (95% CI, 0.79-1.10; I2 = 0) and 0.88 (95% CI, 0.75-1.05; I2 = 0), respectively. We found no publication bias as assessed by Egger's regression asymmetry test, with P = 0.90, 0.28 and 0.60 for the risks of mortality, technique failure and peritonitis in ADPKD patients on PD, respectively. CONCLUSION: Compared with non-ADPKD patients on PD, our study demonstrates that ADPKD patients on PD have 0.68-fold decreased mortality risk. There are no associations of ADPKD status with the risks of technique failure or peritonitis.

Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene (MUC1) mutations (ADTKD-MUC1) is characterized by progressive kidney failure. Genetic evaluation for ADTKD-MUC1 specifically tests for a cytosine duplication that creates a unique frameshift protein (MUC1fs). Our goal was to develop immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations and to identify novel MUC1 mutations in individuals with positive immunohistochemical staining for the MUC1fs protein. METHODS: We performed MUC1fs immunostaining on urinary cell smears and various tissues from ADTKD-MUC1-positive and -negative controls as well as in individuals from 37 ADTKD families that were negative for mutations in known ADTKD genes. We used novel analytic methods to identify MUC1 frameshift mutations. RESULTS: After technique refinement, the sensitivity and specificity for MUC1fs immunostaining of urinary cell smears were 94.2% and 88.6%, respectively. Further genetic testing on 17 families with positive MUC1fs immunostaining revealed six families with five novel MUC1 frameshift mutations that all predict production of the identical MUC1fs protein. CONCLUSIONS: We developed a noninvasive immunohistochemical method to detect MUC1fs that, after further validation, may be useful in the future for diagnostic testing. Production of the MUC1fs protein may be central to the pathogenesis of ADTKD-MUC1.

Clinical problems in hemodialysis patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney. Due to its genetic pattern, the disease differs from other CKD. ADPKD is a multi-system, progressive disorder which is frequently complicated with hypertension, cardiovascular events and cerebrovascular disease. Thus, there are many clinical problems specific to ADPKD. In this article, we reviewed these clinical problems and their management in ADPKD with hemodialysis patients.

Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) can be caused by mutations in the PKD1 or PKD2 genes. The PKD1 gene product is a Wnt cell-surface receptor. We previously showed that a lack of the PKD2 gene product, PC2, increases ß-catenin signaling in mouse embryonic fibroblasts, kidney renal epithelia, and isolated renal collecting duct cells. However, it remains unclear whether ß-catenin signaling plays a role in polycystic kidney disease phenotypes or if a Wnt inhibitor can halt cyst formation in ADPKD disease models. Here, using genetic and pharmacologic approaches, we demonstrated that the elevated ß-catenin signaling caused by PC2 deficiency contributes significantly to disease phenotypes in a mouse ortholog of human ADPKD. Pharmacologically inhibiting ß-catenin stability or the production of mature Wnt protein, or genetically reducing the expression of Ctnnb1 (which encodes ß-catenin), suppressed the formation of renal cysts, improved renal function, and extended survival in ADPKD mice. Our study clearly demonstrates the importance of ß-catenin signaling in disease phenotypes associated with Pkd2 mutation. It also describes the effects of two Wnt inhibitors, XAV939 and LGK974, on various Wnt signaling targets as a potential therapeutic modality for ADPKD, for which there is currently no effective therapy.

Outcome of autosomal dominant polycystic kidney disease patients on peritoneal dialysis: a national retrospective study based on two French registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).

Background: Pathological features of autosomal dominant polycystic kidney disease (ADPKD) include enlarged kidney volume, higher frequency of digestive diverticulitis and abdominal wall hernias. Therefore, many nephrologists have concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to analyse survival and technique failure in ADPKD patients treated with PD. Methods: We conducted two retrospective studies on patients starting dialysis between 2000 and 2010. We used two French registries: the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same parameters were determined for ADPKD patients on PD (n = 797) and compared with those of non-ADPKD patients on PD (n = 12 059). Results: A total of 5291 ADPKD patients and 12 059 non-ADPKD patients were included. Analysis of the REIN registry found that ADPKD patients treated with PD represented 10.91% of the ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher serum albumin levels (38.8 ± 5.3 versus 36.8 ± 5.7 g/dL, P < 0.0001) and were less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD patients was positively associated with the occurrence of a kidney transplantation but not with death [hazard ratio 1.15 (95% confidence interval 0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and better survival. ADPKD status was not associated with an increased risk of technique failure or an increased risk of peritonitis. Conclusions: According to our results, PD is proposed to a selected population of ADPKD patients, PD does not have a negative impact on ADPKD patients' overall survival and PD technique failure is not influenced by ADPKD status. Therefore PD is a reasonable option for ADPKD patients.

Clinical presentation and outcome of autosomal dominant polycystic kidney disease in Nigeria.

INTRODUCTION: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is presumably rare in Africa. Knowledge about the disease in Nigeria is limited as demonstrated by scanty articles on the subject. OBJECTIVES: To determine the pattern of clinical presentation and outcome of ADPKD among ADPKD patients. METHOD: ADPKD subjects were prospectively studied between January 1996 and December 2010. Their demographics, clinical and investigation parameters were documented. Dependency on dialysis, renal transplant and death were the final outcomes. RESULTS: Forty one patients (M:F=1.3:1) with mean age of 48.6±4.6 years were studied. ADPKD was diagnosed at 2.73 cases per annum. Family history of ADPKD and hypertension were present in 56.1% and 82.9% respectively. Their mean systolic and diastolic blood pressures were 166.9 ±23.6 and 104 ±21.2 respectively.Nocturia (78.0%) and loin pain (68.3%) were the most common presenting symptoms. Liver cysts (31.7%) and aortic regurgitation (22.0%) were the predominant extra-renal manifestations.Twenty three (56.1%) received haemodialysis; no renal transplantation. Death rate was 51.2%. Presence of uraemia and intra-cerebral aneurysm contributed significantly to mortality. CONCLUSION: ADPKD may not be so rare in Nigeria. Awareness campaign to change attitude of family members to screening and further studies using newer criteria for diagnosis of ADPKD should be conducted.

A potentially crucial role of the PKD1 C-terminal tail in renal prognosis.

BACKGROUND: Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival. METHODS: We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems. RESULTS: Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G-protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P < 0.0001); renal survival was shorter for mutation positions closer to CTT domain, suggesting its crucial role in renal prognosis. Furthermore, in truncating-type mutations, strong inactivation is anticipated on nucleotides downstream from the mutation site, implying CTT domain inactivation irrespective of mutation site. Shorter mean renal survival was found for PKD1 truncating-type than non-truncating-type mutation carriers (P = 0.0348); mean renal survival was not different between PKD1 3'- and 5'-region truncating-type mutation carriers (P = 0.4375), but was shorter in PKD1 3'-region than in 5'-region non-truncating-type mutation carriers (P = 0.0014). Variable strength of CTT domain inactivation might account for these results. CONCLUSIONS: Aforementioned findings indicate that CTT domain's crucial role in renal prognosis needs further investigation by larger studies (ClinicalTrials.gov; NCT02322385).

Do metabolic derangements in end-stage polycystic kidney disease differ versus other primary kidney diseases?

AIM: Autosomal dominant polycystic kidney disease (ADPKD), a systemic disorder caused by mutation in genes encoding polycystins, has been reported to lead to metabolic derangements including new-onset diabetes mellitus after kidney transplantation. We analyzed markers of insulin resistance (IR), inflammation, nutritional status and insulin-like growth factor-1 (IGF-1) in end-stage renal disease (ESRD) patients with ADPKD and ESRD patients with other primary kidney diseases. METHODS: In a post hoc cross-sectional analysis in 254 non-diabetic CKD 5 patients starting on dialysis, glucose metabolism (insulin, IGF-1, homeostasis model assessment of IR, HOMA-IR), inflammation (high sensitivity C-reactive protein, interleukin-6, and tumour necrosis factor), nutritional status, and bone mineral density (BMD), were assessed. Survival was recorded for median time of 28 months (IQR 15-48 months). RESULTS: Neither indices of IR, nor IGF-1, inflammatory status, nutritional status, or BMD were different in patients with ADPKD as compared to other aetiologies of ESRD. Kaplan-Meier curves showed better survival among the ADPKD group versus other aetiologies, even after an exclusion of diabetic patients. CONCLUSIONS: The ESRD phenotype did not differ in ADPKD versus other primary kidney diseases in terms of markers of IR, inflammation, and nutritional status. This argues against the proposition that ADPKD patients are more prone to develop metabolic derangements beyond those generally observed in advanced CKD. However, additional studies are warranted to further elucidate systemic metabolic aspects of ADPKD.

Peritoneal Dialysis for Patients with Autosomal Dominant Polycystic Kidney Disease.

End-stage renal disease secondary to autosomal dominant polycystic kidney (ADPKD) is a common issue worldwide. Peritoneal dialysis (PD) is a reasonable option for renal replacement therapy for these patients and should not be withheld due to concerns that the patient may not tolerate the fluid volumes in the peritoneal cavity. This review covers the existing data on the outcomes and complications associated with the use of PD in the polycystic kidney disease patient. In general, PD is well tolerated and outcomes in ADPKD patients are equivalent to or better than other patient groups.

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A (n=540; mean eGFR =91±17 ml/min per 1.73 m2) and B (n=462; mean eGFR =48±12 ml/min per 1.73 m2). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. RESULTS: Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m2; P for trend <0.001; Study B: quartile 4, -3.74; 95% confidence interval, -4.14 to -3.34 versus quartile 1, -2.78; 95% confidence interval, -2.92 to -2.63 ml/min per 1.73 m2; P for trend <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m2 did not improve risk prediction. CONCLUSIONS: Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline.

Molecular diagnosis of autosomal dominant polycystic kidney disease.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that accounts for 5-10% of end-stage renal disease in developed countries. Mutations in PKD1 and PKD2 account for a majority of cases. Mutation screening of PKD1 is technically challenging largely due to the complexity resulting from duplication of its first 33 exons in six highly homologous pseudogenes (i.e. PKD1P1-P6). Protocol using locus-specific long-range and nested PCR has enabled comprehensive PKD1 mutation screening but is labor-intensive and costly. Here, the authors review how recent advances in Next Generation Sequencing are poised to transform and extend molecular diagnosis of ADPKD. Areas covered: Key original research articles and reviews of the topic published in English identified through PubMed from 1957-2017. Expert commentary: The authors review current and evolving approaches using targeted resequencing or whole genome sequencing for screening typical as well as challenging cases (e.g. cases with no detectable PKD1 and PKD2 mutations which may be due to somatic mosaicism or other cystic disease; and complex genetics such as bilineal disease).

Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) commonly results in end-stage renal disease (ESRD), yet a long-term treatment that is well tolerated is still lacking. In a small randomized trial in children and adolescents pravastatin administration for 3 years was associated with reduced renal cyst growth, but no large trial has tested the effect of statins in adults. METHODS: We performed a post-hoc analysis of the HALT PKD trials to compare outcomes of participants who never used statins with those who used statin for at least 3 years. Because statins were not randomly allocated, we used propensity score models with inverse probability of treatment weighting to account for imbalances between the groups. For subjects in Study A (preserved renal function, n=438) relevant outcomes were percent change in total kidney and liver volume and the rate of decline in estimated glomerular filtration rate (eGFR); for those in Study B (reduced renal function, n=352) we compared time to the composite endpoint of death, ESRD or 50% decline in eGFR. Follow-up was 5-8 years. RESULTS: There was no difference in any outcome between the 2 groups. However, limitations of this analysis are the small number of statin users in Study A, different statin drugs and doses used, non-randomized allocation and advanced disease stage in Study B. CONCLUSION: Although this post-hoc analysis of the HALT PKD trials does not demonstrate a benefit of statin therapy, conclusions remain preliminary. A larger randomized trial in young people with ADPKD is necessary to answer the question whether statins can slow renal cyst growth and preserve kidney function.