Adult Polycystic Kidney Disease Research Articles

P174Native T1 mapping to assess myocardial fibrosis in adult polycystic kidney disease

P174Native T1 mapping to assess myocardial fibrosis in adult polycystic kidney disease

Correlation of serum galectin-3 level with renal volume and function in adult polycystic kidney disease.

The decrease in kidney functions in autosomal dominant polycystic kidney disease (ADPKD) is strongly correlated with the severity and growth of kidney cysts. Total kidney volume (TKV) was shown to be an early marker of the severity of the disease and a predictor of reduction in kidney functions. New treatment approaches for ADPKD have led to a need for easily applicable strong biomarkers predicting progression of the disease. The profibrotic mediator of galectin-3 (Gal-3) is linked to development of renal fibrosis. The study included 74 patients with ADPKD diagnosis and 40 healthy controls. The TKV of patients was calculated using the manual tracing method on MR images. The serum Gal-3 levels of patient and healthy control groups were measured with the ELISA method. The correlations between serum Gal-3 value with TKV and kidney function were assessed in patients. As the stage of chronic kidney disease (CKD) increased, serum Gal-3 and TKV values increased (p < 0.001, p = 0.049, respectively). Correlation analysis found a negative relationship between serum Gal-3 levels and eGFR (r: -0.515, p < 0.001); however, there was no relationship between serum Gal-3 and TKV (r = 0.112, p = 0.344). Linear regression analysis showed the major parameter affecting Gal-3 was eGFR (p = 0.016). In our study, we showed that renal impairment is an important determinant of Gal-3, and there is no correlation of Gal-3 and TKV in ADPKD. As a result, there is an urgent clinical need for new biomarkers to identify individuals with the chance of treatment in the early stage among ADPKD patients.

Subarachnoid Hemorrhage in Hospitalized Renal Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease: A Nationwide Analysis.

Background: This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. Methods: The 2005–2014 National Inpatient Sample databases were used to identify all hospitalized renal transplant patients. The inpatient prevalence of SAH as a discharge diagnosis between ADPKD and non-ADPKD renal transplant patients was compared. Among SAH patients, the in-hospital mortality, use of aneurysm clipping, hospital length of stay, total hospitalization cost and charges between ADPKD and non-ADPKD patients were compared, adjusting for potential confounders. Results: The inpatient prevalence of SAH in ADPKD was 3.8/1000 admissions, compared to 0.9/1000 admissions in non-ADPKD patients (p < 0.01). Of 833 renal transplant patients with a diagnosis of SAH, 30 had ADPKD. Five (17%) ADPKD renal patients with SAH died in hospitals compared to 188 (23.4%) non-ADPKD renal patients (p = 0.70). In adjusted analysis, there was no statistically significant difference in mortality, use of aneurysm clipping, hospital length of stay, or total hospitalization costs and charges between ADPKD and non-ADPKD patients with SAH. Conclusion: Renal transplant patients with ADPKD had a 4-fold higher inpatient prevalence of SAH than those without ADPKD. Further studies are needed to compare the incidence of overall admissions in ADPKD and non-ADPKD patients. When renal transplant patients developed SAH, inpatient mortality rates were high regardless of ADPKD status. The outcomes, as well as resource utilization, were comparable between the two groups.

Renal Denervation Mitigates Hypertension and Improves Glomerular Filtration Rate in an Adult Rat Model of Polycystic Kidney Disease

Polycystic kidney disease (PKD) remains the most common form of inherited chronic kidney disease failure, and the only cure is renal transplantation. PKD is also strongly associated with increased arterial pressure (AP) and peripheral sympathetic nerve activity (SNA). Recent studies have shown ablation of renal nerves, or renal denervation (RDN), may be effective treatment for varying forms of HTN and renal disease; however, the role and mechanism for renal nerves in preexisting, PKD‐associated renal dysfunction and HTN remain unclear. Therefore, the aim of study was investigate the role of renal nerves in adult PKD, where we hypothesized RDN would reduce AP, lower peripheral sympathetic tone, and improve glomerular filtration rate (GFR) in the adult PKD rat.To test this hypothesis, 6‐month‐old male and female PKD rats underwent bilateral surgical RDN or sham surgery (Total n=18; 9/group; 3M/6F). RDN was achieved by surgical dissection followed by perivascular application of 10%(v/v) phenol. Cardiovascular parameters were recorded by radiotelemetry which was implanted two weeks prior to experimental treatment. Peripheral sympathetic tone was estimated by depressor response to acute ganglionic blockade (GB). GFR was assessed in unrestrained, conscious rats by acute FITC‐sinistrin clearance. Two weeks following RDN/Sham, rats were euthanized and tissues were collected for further analysis. Data was analyzed by a two‐way ANOVA, across sex and treatment groups (α=0.05). Data presented as mean+SEM.At baseline, no differences in 24‐hour mean AP (132 ± 2 vs. 129 ± 3mmHg), acute GB response (39 ± 3 vs. 42 ± 4ΔmmHg), nor GFR (0.93 ± 0.06 vs. 0.91 ± 0.04 mL/min/100g) were detected between treatment groups. No sex differences at baseline were detected at baseline. Two weeks following treatment, 24‐hour mean AP was lowered in RDN (121 ± 1.5mmHg) vs. sham (130 ± 2.8ΔmmHg), and no effect of sex was observed. Similarly, depressor response to GB was halved in RDN (−16 ± 2 ΔmmHg) compared to sham (−32 ± 3 ΔmmHg), and no effect of sex was detected. GFR was significantly increased in RDN vs. sham (1.18 ± 0.06 vs. 0.84 ± 0.08 mL/min/100g), and no effect of sex was detected. Lastly, no difference in renal cystic index was detected between RDN and sham (8.27 ± 1.39 vs. 8.74 ± 0.90%), and differences between male and female groups were observed.Together, these data support our initial hypothesis, where RDN effectively lowered AP and peripheral sympathetic tone in the PKD rat. This was paired with a significant increase in GFR in these animals, indicating an improvement in renal function despite no observable effect on renal cystic index Of note, the efficacy of RDN was similar across male and female groups. Further studies are underway to determine if the cardiovascular and renal effects observed in this study are primarily mediated by the ablation of the efferent or afferent nerves.Support or Funding InformationThis project was supported in part by NIH 1K99HL141650 (CTB) and R01HL116476 (JWO).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Multifocal renal cell carcinoma associated with multiple simple renal cysts: A rare presentation

Multifocal renal cell carcinoma associated with multiple simple renal cysts: A rare presentation - ACHR- Print ISSN No: - 2581-5725 Online ISSN No:- 2456-9267 Article DOI No:- 10.18231/2456-9267.2019.0016, IP Archives of Cytology and Histopathology Research-IP Arch Cytol Histopathol Res

MRI Screening for Cerebral Aneurysm in Adult Polycystic Kidney Disease: Is the Money Worth Spending?

MRI Screening for Cerebral Aneurysm in Adult Polycystic Kidney Disease: Is the Money Worth Spending?

Hypertension in adult polycystic kidney disease: a narrative review

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disorder that impacts approximately 12 million worldwide. It is characterized by bilateral kidney enlargement and cystic growth. Hypertension (HTN) is a focal point in the management of ADPKD and is linked to a faster progression to end stage renal disease. Current novel therapies have proven to reduce the progression of renal damage. The ideal goal is to minimize risk through preventative studies and pharmacology to further increase life expectancy and quality. The purpose of this article is to highlight the importance of blood pressure management in ADPKD and review current literature to determine the most effective preventative pharmacotherapy.

The comorbidity profile among chronic kidney disease patients in clinical practice: A prospective study

Background: The comorbidity profile among chronic kidney disease (CKD) patients can influence and predispose them to increase mortality and health-care costs. In addition, there could also be a prolongation in the length of hospital stay and recurrent frequency of hospitalization. Aim: This study was predominantly designed to highlight and create awareness concerning the burden of comorbidity profile among CKD patients in renal practice. Materials and Methods: This was a descriptive prospective study of 18-month duration that was carried out to review the medical case records of consented adult CKD patients attending a Nigerian Tertiary Kidney Care Hospital from January 2015 to June 2016. Results: This study involved 123 consented adult CKD patients comprising 82 (66.67%) males and 41 (33.33%) females, with a mean age of 53.81 ± 16.03 years. A majority of the respondents 45 (36.59%) were having 2 comorbidities with hypertension in 103 (83.70%), diabetes mellitus in 39 (31.70%), obesity in 24 (19.51%), heart failure in 11 (8.90%), obstructive uropathy in 8 (6.50%), human immunodeficiency virus infection in 7 (5.70%), peptic ulcer disease/gastroesophageal reflux disease in 7 (5.70%), gastroenteritis/gastrointestinal tract sepsis in 6 (4.9%), stroke in 5 (4.10%), adult polycystic kidney disease in 5 (4.10%), and hepatitis B virus infection in 5 (4.10%), being the most frequent. Eighty-six (69.9%) patients were in CKD Stage 5, 15 (12.2%) were in CKD Stage 4, 19 (15.5%) were in CKD Stage 3, 2 (1.6%) in CKD Stage 2, and the remaining one (0.8%) in CKD Stage 1. Regarding the form of nephrological interventions offered, majority of the respondents 66 (53.66%) were on maintenance dialysis, followed by 53 (43.09%) on conservative care, while 4 (3.25%) were on renal graft transplant. Conclusion: The prevalence rates for comorbidities such as hypertension, diabetes mellitus, and obesity were significantly high among these CKD patients; this agreed with the previous studies conducted in other regions of the world. In this study, the comorbidity profile among CKD patients may significantly increase the risk of mortality, recurrent frequency of hospitalization, length of hospital admission, and health-care costs.

Polycystosis of the renal sinus or polycystic kidney disease. Controversies, challenges and history of a shared discovery

ObjectiveTo recall the history of the discovery of non-nephron cystic disease, detected simultaneously in 2 hospitals in Madrid, and the vicissitudes that the authors endured during the process of recognizing this disease, while being ignored by the international scientific literature. Material and methodWe analyzed the authors’ first publications and presentations, their correspondence relaying the difficulties in reporting the confusion with adult polycystic kidney disease (APKD) and the subsequent nosological identification of the process. We consulted with individuals who worked with the 2 authors to increase the accuracy and objectivity of the history report. ResultsWe confirmed the authors’ remarkable efforts in getting the process definitively recognized despite the notable difficulties. ConclusionsRigorous clinical observation recognizes processes ignored by the medical literature, and the correct application of the scientific method helps identify and reveal new nosological entities, confirming with this story's example that, in medicine, there are no exhausted issues.

A Study of the spectrum of Urinary Tract infections in patients with Adult Polycystic Kidney Disease – An old problem with a better outcome

A Study of the spectrum of Urinary Tract infections in patients with Adult Polycystic Kidney Disease – An old problem with a better outcome

Role of calcium in adult onset polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in genes encoding the polycystin (PC) 1 and 2 proteins. The goal of this study was to determine the role of calcium in regulating cyst growth. Stromal interaction molecule 1 (STIM1) protein expression was 15-fold higher in PC1-null proximal tubule cells (PN) than in heterozygote (PH) controls and 2-fold higher in an inducible, PC1 knockout, mouse model of ADPKD compared to a non-cystic match control. IP3 receptor protein expression was also higher in the cystic mice. Knocking down STIM1 with siRNA reduced cyst growth and lowered cAMP levels in PN cells. Fura2 measurements of intracellular Ca2+ showed higher levels of intracellular Ca2+, SOCE and thaspigargin-stimulated ER Ca2+ release in PN vs. PH cells. There was a dramatic reduction in thapsigargin-stimulated release of ER Ca2+ following STIM1 silencing or application of 2-APB, consistent with altered ER Ca2+ movement; the protein expression of the Ca2+-dependent adenylyl cyclases (AC) AC3 and AC6 was up- and down-regulated, respectively. Like STIM1 knockdown, application of the calmodulin inhibitor W7 lowered cAMP levels, further indicating that STIM1 regulates AC3 via Ca2+ We conclude that the high levels of STIM1 in ADPKD cells play a role in supporting cyst growth and promoting high cAMP levels and an increased release of Ca2+ from the ER. Thus, our results provide novel therapeutic targets for treating ADPKD.

Abstract P119: Hypertension and Renal Dysfunction Are Mitigated by Surgical Renal Denervation in an Adult Rat Model of Polycystic Kidney Disease

Polycystic kidney disease (PKD) is the most common form of inherited chronic kidney disease failure. PKD is also associated with hypertension (HTN) and increased peripheral sympathetic activity (SNA). Recent studies have shown ablation of renal nerves may be effective treatment for varying forms of HTN and renal disease; however, the role and mechanism for renal nerves in PKD-associated renal dysfunction and HTN are unclear. Therefore, this study was conducted to test the hypothesis that renal denervation (RDN) would reduce AP, lower peripheral SNA, and improve renal function in the adult PKD rat. To test this hypothesis, 6-month-old male and female PKD rats underwent bilateral surgical RDN or sham surgery (Total n=18; 9/group; 3M/6F). Cardiovascular parameters were monitored by implanted radiotelemeter. Peripheral sympathetic tone was estimated by depressor response to acute ganglionic blockade (GB). Renal function was assessed by measuring glomerular filtration rate (GFR) by FITC-sinistrin clearance. Two weeks following treatment, rats were euthanized and tissues were collected for further analysis. Data was analyzed by a two-way ANOVA, across sex and treatment groups (α=0.05). Data presented as mean+SEM. At baseline, no differences in mean AP (132±2 vs. 129±3 mmHg), GB response (39±3vs. 42±4 ΔmmHg), nor GFR (0.93±0.06 vs. 0.91±0.04 mL/min/100g) were detected between RDN vs. sham. Two weeks following treatment, AP was lower in RDN (120±2mmHg) vs. sham (128±3mmHg). Similarly, GB was halved in RDN (-16±2 ΔmmHg) compared to sham (-32±3 ΔmmHg). GFR was increased in RDN rats vs. sham (1.18±0.06 vs. 0.84±0.08 mL/min/100g). Lastly, no difference in renal cystic area was detected between RDN and sham (8.27±1.39 vs. 8.74±0.90 %). No effect of sex was detected in any of the reported measurements. Altogether, these data support our initial hypothesis, where RDN effectively lowered AP and peripheral sympathetic tone in the PKD rat. Interestingly, we also observed a substantial increase in GFR in these animals, indicating an improvement in renal function despite no observable effect on cystic area. Of note, RDN was effective in both males and female rats. Further studies using repeated measurements are required to elucidate the order in which these effects occur.

Poliquistosis del seno renal o hilioquistosis. Controversias, retos e historia de un descubrimiento compartido

ObjectiveTo recall the history of the discovery of non-nephron cystic disease, detected simultaneously in 2 hospitals in Madrid, and the vicissitudes that the authors endured during the process of recognising this disease, while being ignored by the international scientific literature. Material and methodWe analysed the authors’ first publications and presentations, their correspondence relaying the difficulties in reporting the confusion with adult polycystic kidney disease (APKD) and the subsequent nosological identification of the process. We consulted with individuals who worked with the 2 authors to increase the accuracy and objectivity of the history report. ResultsWe confirmed the authors’ remarkable efforts in getting the process definitively recognised despite the notable difficulties. ConclusionsRigorous clinical observation recognises processes ignored by the medical literature, and the correct application of the scientific method helps identify and reveal new nosological entities, confirming with this story's example that, in medicine, there are no exhausted issues.

Study of two pedigrees affected with adult polycystic kidney disease and male infertility resulting from novel mutations of PKD1

To explore the genetic etiology of two Chinese pedigrees affected with autosomal dominant adult polycystic kidney disease and male infertility. The coding regions of the PKD1 and PKD2 genes were subjected to PCR and Sanger sequencing. Suspected pathogenic mutations were analyzed by pedigree analysis and bioinformatics analysis. Mutation screening was performed using Sanger sequencing of blood samples obtained from 50 healthy individuals. Two novel heterozygous mutations, c.6953_6977 del(p.Arg2318Hisfs*15) and c.10937T>G (p.Val3646Gly) of the PKD1 gene were identified in the affected members of the two pedigrees, respectively, but not among to normal family members of the two pedigrees. Pedigree and bioinformatics analysis showed that both mutations were pathogenic. No pathological mutations were found in the cohort of 50 healthy individuals. Two novel mutations, c.6953_6977del(p.Arg2318Hisfs*15) and c.10937T>G (p.Val3646Gly) of the PKD1 gene may be responsible for the disease in the two pedigrees, which have enriched the spectrum of PKD1 gene mutations and provided a basis for genetic counseling and prenatal disgnosis.

The association of serum angiogenic growth factors with renal structure and function in patients with adult autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is a common congenital chronic kidney disease (CKD). We report here the relationship of serum angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) with total kidney volume (TKV), total cyst volume (TCV), and renal failure in adult ADPKD patients at various stages of CKD. This cross-sectional study was conducted with 50 patients diagnosed with ADPKD and a control group of 45 age-matched healthy volunteers. In patient group, TKV and TCV were determined with upper abdominal magnetic resonance imaging, whereas in controls, TKV was determined with ultrasonography according to ellipsoid formula. Renal function was assessed with serum creatinine, estimated glomerular filtration rate (eGFR), and spot urinary protein/creatinine ratio (UPCR). Ang-1, Ang-2, and VEGF were measured using enzyme-linked immunosorbent assay. Patients with ADPKD had significantly higher TKV (p < 0.001) and UPCR (p < 0.001), and lower eGFR (p ≤ 0.001) compared to the controls. Log10Ang-2 was found to be higher in ADPKD patients at all CKD stages. Multiple linear regression analysis showed that there was no association between log10Ang-1, log10Ang-2, or log10VEGF and creatinine, eGFR, UPCR, log10TKV (p > 0.05). There was no association of serum angiogenic growth factors with TKV or renal failure in ADPKD patients. Increased serum Ang-2 observed in stages 1-2 CKD suggests that angiogenesis plays a role in the progression of early stage ADPKD, but not at later stages of the disease. This may be explained by possible cessation of angiogenesis in advanced stages of CKD due to the increased number of sclerotic glomeruli.

Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.

Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients.

Prevalence of clinically validated primary causes of end-stage renal disease (ESRD) in a State Capital in Northeastern Brazil.

ABSTRACTIntroduction:Knowledge of validated primary causes of end-stage renal disease (ESRD) is extremely relevant in the realm of public health. The literature lacks validated studies on the primary causes of ESRD.Objective:The aim of this study was to estimate the prevalence of the causes of ESRD in a State Capital in Northeastern Brazil.Methods:This cross-sectional study was based on the analysis of medical records of patients on hemodialysis at five specialized centers in Fortaleza, CE, Brazil. Deaths and patients referred to other centers outside Fortaleza were excluded from the study. The data of 830 patients were initially collected, but 818 remained enrolled after the exclusion criteria were applied, the equivalent to 48% of the patents on dialysis in the city.Results:61.1% of the patients were males. Twenty-two percent of all enrolled individuals were aged 60-69 years. Patient mean age was 55.7 ± 16 years. The most common validated cause of ESRD was unknown (35.3%), followed by diabetes mellitus (26.4%), adult polycystic kidney disease (6.2%), graft failure (6.2%), obstructive uropathy (5.7%), and primary glomerulonephritis (5.3%). Before validation, primary hypertension was the most frequent cause of chronic kidney disease (22.9%), decreased to 3.8% after validation.Conclusion:The data contradicted national studies reporting primary hypertension as the main cause of chronic kidney disease (CKD). A high rate of unknown causes and categorization bias were observed mainly in relation to primary hypertension as a cause of CKD, which affects the overall prevalence of causes of ESRD in patients on dialysis.

A Successful Kidney Transplant for a Case of LMX1B Gene Mutation with a Positive Family History of Polycystic Kidney Disease

Nail-Patella syndrome is pleiotropic autosomal dominant disorder characterized by skeletal abnormalities and frequently renal disease. In this case report genetic analysis revealed a pathogenic heterozygous missense mutation of the LMX1B gene as c.[737G>A], p.([Arg246Gln)]. This variant is predicted to cause substitution of a basic arginine residue for a polar uncharged glutamine residue at position 246. The nucleotide at position 737 and amino acid at position 246 are both highly conserved across species. Although LMX1B mutation causing hereditary focal segmental glomerulosclerosis (FSGS) without any extra-renal involvement has been described as nail patella like renal disease (NPLRD) where there is partial impairment of transcriptional activity with these mutations leading to absence of other features of nail patella syndrome (NPS). Our case report gets interesting as patient had progressed relatively quickly to end stage renal disease. Some of heterozygous gene mutation FSGS cases are expected to recur after kidney transplantation. Our case has received a successful renal transplant from brother which is working well for the last 3 years without any evidence of recurrence. Another interesting feature of our case was the strong family history of unrelated other renal genetic disorder autosomal dominant adult polycystic kidney disease (ADPKD).

Case Report: an unusual cause of cyst infection in adult polycystic kidney disease (ADPKD)

Case Report: an unusual cause of cyst infection in adult polycystic kidney disease (ADPKD)

Use of targeted sequence capture and high-throughput sequencing identifies a novel PKD1 mutation involved in adult polycystic kidney disease

Polycystic kidney disease (PKD) is a common inherited disease that is characterized by a progressive development of renal cysts. Approximately 85% of PKD cases are due to mutations in the polycystin 1 (PKD1) gene. Here, we report a pedigree containing nine patients with autosomal dominant PKD (ADPKD). Using targeted exome sequencing of PKD1 and PKD2 genes, we identified a novel heterozygous frameshift mutation c.3976_3977insCT (p.F1326Sfs*21) in the PKD1 gene that segregated between affected and unaffected family members. This mutation is currently not present in the 1000 Genomes Project nor ExAC databases and is therefore a novel PKD1 mutation involved in ADPKD. These results provide a novel sequence variant for the genetic analysis of this disease.