Polycystic Kidney Disease Patients Research Articles

#654 Double-blind randomised controlled trial of nitrate-replete beetroot juice on blood pressure in autosomal dominant polycystic kidney disease

Abstract Background and Aims Hypertension in autosomal dominant polycystic kidney disease is in part mediated by reduced polycystin-regulated nitric oxide synthase activity. In this study, the hypothesis that beetroot juice (BRJ, a rich natural dietary source of nitrate) reduces blood pressure in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients was evaluated. Method Stable hypertensive patients (n = 60) with ADPKD (eGFR > 30 mL/min/1.73 m2) were randomised (1:1) to either nitrate-replete BRJ (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. Patients and investigators were blinded to the allocation. The primary endpoints were changes in systolic and diastolic clinic blood pressure between baseline and at 4 weeks. The secondary endpoints were serum nitrate/nitrite levels, daily home blood pressure and albuminuria. Results Serum nitrate/nitrite increased 3.6-fold in the nitrate-replete compared to the nitrate-deplete group (p < 0.01). Both groups had similar baseline characteristics. After 4 weeks, clinic systolic and diastolic blood pressure significantly declined in both nitrate-replete and nitrate-deplete BRJ groups compared to baseline (systolic blood pressure: −5.36 vs. −7.65 mmHg; diastolic blood pressure: −3.55 vs. −2.73 mmHg; P < 0.05). Other secondary endpoints, treatment adherence, discontinuations and adverse effects were similar in both groups. Conclusion Increasing serum nitrate with BRJ did not lower blood pressure in hypertensive patients with ADPKD. The blood pressure reduction in both groups could be due to non-nitrate phytonutrients in BRJ and/or placebo-associated effects. These data further emphasise the importance of healthy eating and regular monitoring of blood pressure in patients with ADPKD.

#2048 Exploring somatic mutation mechanisms in pre-cystic renal cells of autosomal dominant polycystic kidney disease patients

Abstract Background and Aims Genetic changes accumulate in our cells during a lifetime, at a rate that varies according to cell type and mutagen exposure [1]. Somatic mutations are the driving force of cancer and contribute to “second hit” disorders, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD). ADPKD is caused by inherited mutations that disrupt one allele of PKD1 or PKD2 genes. Somatic loss of the second allele triggers tubule cell clonal expansion and the formation of renal cysts. Given the high number of cysts that form during a lifetime, somatic mutation rates may be abnormally high in the kidney of ADPKD patients. The identification of factors enhancing somatic mutation rates can lead to preventive strategies to limit cyst formation. Metabolic alterations, i.e. increased glutamine utilization and reduced urea cycle, have been shown to induce somatic mutations in cancer [2]. Loss of urea cycle increases pyrimidine synthesis, which unbalances the nucleotide pools and results in a distinct signature of single base substitutions (SBSs) [1]. Similar metabolic changes have been observed in ADPKD [3, 4]. Thus, we sought to test metabolism-driven somatic mutagenesis in pre-cystic kidneys and its contribution to second hit mutations in ADPKD. Method We clonally expanded normal kidney cells from human urine samples and performed a gene expression study by qPCR. We studied 31 clones from 4 ADPKD patients (age range: 25-45) with truncating mutations in PKD1 and normal kidney function, despite a clear cystic phenotype. ADPKD cells were compared to 55 clones from 5 healthy volunteers (age range: 24-53), and 32 clones from 6 patients with another cystic kidney disease, Von Hippel Lindau disease (VHL; age range: 29-56). A subset of clones (n = 19 controls, n = 12 ADPKD) was subjected to whole genome sequencing and somatic mutation analysis. Results Urines of ADPKD patients contained higher numbers of cells that expanded in vitro, compared to both control (p = 0.0008) and VHL individuals (p = 0.01). Gene expression analyses showed that irrespective of genetic background, all cultured clones originated from the kidney tubule epithelium (high PAX2 and PAX8), and some originated from damaged tubules (VCAM1, KIM1). We tested the hypothesized metabolic rewiring by analyzing expression levels of enzymes involved in glutamine utilization, urea cycle, and pyrimidine biosynthesis. Except for ASNS (Asparagine Synthetase), which was higher in ADPKD vs control clones (p = 0.0098), no gene-expression differences were observed. However, clones from ADPKD patients showed signs of the metabolic rewiring responsible for increased pyrimidine production, i.e. a positive correlation (r = 0.691; p < 0.0001) between urea cycle enzymes downregulation and upregulation of the pyrimidine synthesis enzyme CAD. Since excessive pyrimidines lead to mutation [2], we analyzed the number of somatic SBSs per genome, after filtering for germline variants. We did not find increased mutation rates in ADPKD compared to controls, but an analogous, linear increase of mutations with age and similar levels of the pyrimidine-rich mutational signature. Conclusion Urine-derived kidney tubule epithelial cells with heterozygous truncating mutations in PKD1 exhibit certain characteristics of metabolic reprogramming typical of kidneys from ADPKD patients with advanced pathology. Nevertheless, in the limited number of pre-cystic cells that we have analyzed, this metabolic reprogramming did not translate into an excess of somatic mutations.

The Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity

The main characteristic of polycystic kidney disease (PKD) is the development of multiple fluid filled renal cysts. The discovery of mislocated Na, K-ATPase in the apical membrane of cyst lining epithelia alluded to a reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na, K-ATPase in cysts remains controversial with some investigators finding conventional localization in cysts. Thus, we investigated localization of the Na, K-ATPase and assessed the apical-basolateral polarization of cyst lining epithelia by means of immunohistochemistry on tissue from six anonymous PKD patients undergoing nephrectomy. The Na, K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical t-SNARE protein Syntaxin-3 also immunolocalized to the apical domain of cyst lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst lining epithelia in polycystic kidney disease. This study was supported by Aarhus University Research Foundation(AUFF) AU-Ideas, and the Danish Council for Independent Research—MedicalSciences. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Quantitative susceptibility mapping for detection of kidney stones, hemorrhage differentiation, and cyst classification in ADPKD.

The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. QSM visualized two renal calcifications measuring 9 and 10mm and three pelvic phleboliths measuring 2mm but missed 24 calcifications measuring 1mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.

Prevalence and outcomes of polycystic kidney disease in African populations: A systematic review.

Polycystic kidney disease (PKD) is the most common genetic cause of kidney disease. It is a progressive and irreversible condition that can lead to end-stage renal disease and many other visceral complications. Current comprehensive data on PKD patterns in Africa is lacking. To describe the prevalence and outcomes of PKD in the African population. A literature search of PubMed, African journal online, and Google Scholar databases between 2000 and 2023 was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed to design the study. Clinical presentations and outcomes of patients were extracted from the included studies. Out of 106 articles, we included 13 studies from 7 African countries. Ten of them were retrospective descriptive studies concerning 943 PKD patients with a mean age of 47.9 years. The accurate prevalence and incidence of PKD were not known but it represented the third causal nephropathy among dialysis patients. In majority of patients, the diagnosis of the disease was often delayed. Kidney function impairment, abdominal mass, and hypertension were the leading symptoms at presentation with a pooled prevalence of 72.1% (69.1-75.1), 65.8% (62.2-69.4), and 57.4% (54.2-60.6) respectively. Hematuria and infections were the most frequent complications. Genotyping was performed in few studies that revealed a high proportion of new mutations mainly in the PKD1 gene. The prevalence of PKD in African populations is not clearly defined. Clinical symptoms were almost present with most patients who had kidney function impairment and abdominal mass at the diagnostic. Larger studies including genetic testing are needed to determine the burden of PKD in African populations.

Native nephrectomy in polycystic kidney disease patients on transplant lists: how and when?

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease, accounts for approximately 10% of the patients on kidney transplantation waitlists.High rates of complications including hemorrhage, infections, nephrolithiasis and kidney size-related compressive complaints have been reported among ADPKD patients. Therefore, the need for routine native nephrectomy and timing of such procedure in ADPKD patients being prepared for transplantation are debated. Even though pre-transplant nephrectomy has the potential to provide fewer infectious complications due to lack of immunosuppressive medication use, such procedure has been associated with longer hospital stay, loss of residual kidney function and need for dialysis. Although simultaneous nephrectomy and transplantation could potentially lead to longer perioperative duration, perioperative complications and need for blood transfusions, this was not confirmed in cohort studies. Therefore, some institutions routinely perform simultaneous unilateral nephrectomy and kidney transplantation. In this narrative review, our aim is to evaluate the current evidence regarding the need andtiming of nephrectomy in ADPKD patients in relation to kidney transplantation.

HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.MethodsThe HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care.OutcomesThe primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume.ConclusionThe HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.

The Cyst Epithelium in Polycystic Kidney Disease Patients Displays Normal Apical-Basolateral Cell Polarity.

The main characteristic of polycystic kidney disease is the development of multiple fluid-filled renal cysts. The discovery of mislocalized sodium-potassium pump (Na,K-ATPase) in the apical membrane of cyst-lining epithelia alluded to reversal of polarity as a possible explanation for the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst-lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical targeting protein Syntaxin-3 also immunolocalized to the apical domain of cyst-lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Thus, no deviations from the typical epithelial distribution of basic cell polarity proteins were observed in the cysts from the six patients. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst-lining epithelia in polycystic kidney disease.

Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as "metformin" and "ADPKD". MA was conducted using the Cochrane Collaboration's RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK). We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts. Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts.

Monoallelic IFT140 Pathogenic Variants in Adult Polycystic Kidney Disease Patients Without Family History

Monoallelic IFT140 Pathogenic Variants in Adult Polycystic Kidney Disease Patients Without Family History

Comprehensive Approach to the Polycystic Kidney Disease Patient: Clinical and Therapeutic Strategies in the Management of a Multifaceted Pathology

Polycystic kidney disease (PKD) is a heterogeneous, inherited clinical entity characterized by the formation of renal cysts, which can manifest with a wide range of symptoms and complications. This article comprehensively reviews advances in the diagnosis and treatment of PKD, highlighting the importance of a multidisciplinary approach ranging from primary care to specialized care in nephrology and urology. Management strategies for major symptoms such as low back pain, hypertension, and urologic complications are discussed, as well as the most recent therapeutic options, including vasopressin inhibitors and ongoing clinical trials. Furthermore, it highlights the relevance of patient education and early detection in the management of this pathology, in order to improve the quality of life and survival of patients with PKD. This article provides a comprehensive overview of the management of PKD, with a focus on the latest research and therapies, to guide health care professionals in making informed clinical decisions and providing patients with high-quality care in the context of this complex renal disease.

Abstract P369: The Role Of Primary Cilia In The Pathogenesis And Therapy Of Hypertension In Polycystic Kidney Disease.

Primary cilia are sensory organelles, extending from the surface of vascular endothelialcells. Primary cilia dysfunctions have been linked to numerous genetic disorders,including polycystic kidney disease (PKD). Although PKD is characterized by fluid-filledcystic kidneys, cardiovascular complications such as hypertension (HTN) are the leadingcause of death in PKD patients. We demonstrated that primary cilia sense and transmitexternal mechanical stimuli such as fluid shear stress into internal biochemical reactionssuch as the release of nitric oxide (NO). This idea has only been investigated in ECs invitro . However, the importance of the vascular primary cilia in the long-term regulationof BP has not been investigated. NO-induced vasodilation is also produced in response tostimulation of eNOS by muscarinic acetylcholine receptor 3 (AChM3R) activation byacetylcholine (ACh). Using immunofluorescence staining, we generated new andsurprising data showing that AChM3R, and its signaling components, PIP2 are localizedto primary cilia and can modulate cilia function. We hypothesize that primary ciliacontribute to BP regulation in PKD through AChM3R. We showed that both, selective(cevimeline) and non-selective (ACh, CCh) activation of AChM3R led to an increase incilia length and cilia sensory function in terms of p-eNOS expression. We also generatedendothelial-specific ( Tie2Cre and VECre ) AChM3R KO mouse lines, in which AChM3R was deleted from the vascular endothelia. These mice developed high BP, as measured bytail cuff and telemetry blood pressure monitoring devices, associated with attenuated NOproduction and impaired vascular relaxation in response to ACh stimulation. Thesestudies demonstrated the physiological significance of primary cilia-derived NO in thelong-term control of vascular hemodynamics.

643 A Review of the Screening Protocols Investigating Intracranial Aneurysms in Polycystic Kidney Disease

Abstract Aim Intracranial aneurysms (ICA) are a common complication of polycystic kidney disease (PKD). Due to the lack of screening protocols that exist for PKD patients, without the appropriate preventative measures ICA rupture leads to significant morbidity and mortality. The aim is to analyse existing screening protocols by referencing the lead time between ICA diagnosis and rupture in PKD patients, the purpose and importance of screening, the types of imaging modalities used, and patient outcomes. We will also consider cost-effectiveness and its relation in establishing a screening protocol. Method A literature search was conducted in April 2022 for articles published between 1990-2022 with special interest in ICA, PKD, and screening protocols. Only exclusion criteria were patients who were diagnosed with PKD <30 years of age. An independent reviewer screened the relevant full papers prior to inclusion. Results Our findings suggest that if a PKD presents with either a positive family history of ICA and/or cerebrovascular events and/or is above 40 years of age, then they should have a magnetic resonance angiography (MRA) scan every 5 years to monitor ICA development with annual follow-ups. This will significantly decrease patient morbidity and mortality in PKD positive patients. Conclusions While there is significant evidence proving that screening protocols decrease the morbidity and mortality of PKD patients, none have been suggested. The screening protocol suggested in this review should be used as a guideline for future studies that will try and establish a national or international guidelines that can be used by nephrologists and neurosurgeons worldwide.

Susceptibility of Developing Renal and Lung Cancer in Polycystic Kidney Disease Patients: An Evidence in Reaching Consensus

Objective. The association between Polycystic Kidney Disease (PKD) and susceptibility to developing oncogenicity states remains controversial, and no consensus has yet been reached. Large-scale studies on this association are also lacking. Therefore, we identified the risk of developing cancer in PKD patients. Methods. Patients diagnosed with PKD between 2000 and 2010 were enrolled in the National Health Insurance Research Database (NHIRD)-derived Longitudinal Health Insurance. Patients with antecedent cancer, end-stage renal disease, or those diagnosed with cancer within one year were excluded. Using a Standardized Incidence Ratio (SIR), we compared the patterns of cancer incidence in PKD patients and the general population. Results. The entire cohort was observed for 8,014 people, and a total of 1820 PKD patients were included, and after a median follow-up of 4.43 years, 82 patients developed cancer. Though the risk of overall cancers was comparable between PKD patients and the general population, the PKD patients exhibited a higher risk of kidney malignancy (SIR 3.72, 95% CI 1.60∼7.33). The female PKD patients were at a higher risk of lung and mediastinal cancer (SIR: 2.83, 95% CI 1.03∼6.16). The subgroup analysis revealed a significantly higher risk of kidney cancer in the patients aged <65 years (SIR 7.39, 95% CI 1.99∼18.93) than those elderly patients, especially in the females (SIR 9.81, 95%1.10∼35.41, p < 0.05 ). The multivariate analysis showed significant risk factors for cancer among the PKD population, including 1-year age (HR 1.04; 95% CI 1.02–1.06; p < 0.001 ), male gender (HR 1.85; 95% CI 1.14–3.00; p = 0.012 ), and chronic liver disease (HR 2.03; 95% CI 1.31–3.13; p < 0.001 ). Conclusion. PKD patients may be more susceptible to developing renal, lung, and mediastinal cancer than the control population, which might be attributed to PKD genetic instability.

The Efficacy, the Treatment Response and the Aquaretic Effects of a Three-Year Tolvaptan Regimen in Polycystic Kidney Disease Patients.

Tolvaptan, a selective vasopressin V2 receptor antagonist, is the first and only approved specific treatment for Autosomal-Dominant Polycystic Kidney Disease (ADPKD), and is used in current clinical practice. Real clinical data are missing. In this retrospective study, 41 ADPKD patients received tolvaptan for 3 years, from 2018 to 2021. Total kidney volume (TKV) was measured using Magnetic Resonance Imaging, at initiation and at the end of the treatment period. A complete biochemistry/hematology profile and a 24 h urine volume collection were performed monthly for the first 18 months and every 3 months thereafter. At the end of the treatment period, the median (IQR) estimated Glomerular Filtration Rate (e-GFR) was 5.3 (-1.3, 8.7) mL/min higher than the expected e-GFR decline without treatment, while the prediction for End Stage Chronic Kidney Disease (ESKD) had been prolonged by 1 (0, 2) year. Total Kidney Volume did not change significantly (2250 (1357) mL at 3 years of treatment vs. 2180 (1091) mL expected without treatment, p = 0.48). Younger patients with a relatively preserved e-GFR, lower hypertension burden, better familiar renal prognosis and more severe imaging data showed better outcomes. The aquaretic adverse effects of tolvaptan did not affect renal function and electrolyte balance in 51 patients, in a follow-up period of 18 months. Consequently, tolvaptan seems to be effective in preventing progression of ADPKD when administered in a timely manner in patients with better familiar renal history, shorter hypertension duration and worse imaging profile. Increased diuresis does not affect treatment efficacy.

Are you ready to accompany autosomal dominant polycystic kidney disease patients in their treatment journey? Real practice for selecting rapid progressors and treatment with tolvaptan

Tolvaptan treatment is costly, often accompanied by aquaresis-related adverse events, and requires careful monitoring by medical staff due to the possibility of hepatotoxicity. Nevertheless, it is the only disease-modifying drug to date that has been shown to successfully delay renal replacement therapy. For more patients to receive proper treatment, medical doctors, the rest of the medical team, and the patient must all work together. This paper reviews parameters that can help identify rapid autosomal dominant polycystic kidney disease progressors, who are the target of tolvaptan therapy. It is expected that these parameters will help nephrologists learn practical prescription methods and identify patients who can benefit from tolvaptan treatment. Although several strategies can be used to find rapid progressors, the present review focuses on a practical method to identify rapid progressors according to the presence or absence of evidence and the factors associated with rapid progression based on the Mayo image classification.

#4913 ANALYSIS OF THE LIPID PROFILE IN THE RENAL PATIENT AND SUB-ANALYSIS OF THE POPULATION WITH POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Dyslipidemia is frequent in patients with chronic kidney disease (CKD), it constitutes a factor of progression of both cardiovascular risk (CVR) and CKD itself. It has its own characteristics, which are modified with the ERC stadium. The subgroup of patients with Polycystic Kidney Disease (PKD) presents its own characteristics. The aim of the study was to analyze the lipid profile in the renal population and the differences in the PKD group. Method Retrospective observational study, includes population under follow-up in nephrology consultations in a health area, during 2018–2021. We analyzed lipid profile, renal function and whether they received statins. IBM SPSS Statistics V24 was used. Results 3301 prevalent patients with kidney disease were collected, excluding those on renal replacement therapy (RRT), with glomerular filtration rate (GFR), glomerular filtration rate (GFR) <10ml/min/1.73m² and proteinuria greater than 1.5g. Of these, 112 (3.4%) patients had PKD. 51% of the total CKD patients were under treatment with statins. The average number of Total Cholesterol (TC) was 170.4+/-43mg/dl, LDL 92.3+/-37mg/dl, HDL 50.3+/-15mg/dl and triglycerides (TG) 147.3+/-92mg/dl. In 37% of CKD patients, LDL was >100mg/dl and only 35% had LDL<75mg/dl. In the CKD group with a GFR <60ml/min/1.73m² (N = 2337; 71%), there was a high prevalence of patients with LDL values >100mg/dl (N = 784; 33.5%). In the case of GFR <30ml/min/1.73m² (N = 981; 29.7%), the presence of LDL>100mg/dl 30% (N = 297) was also frequent. In the subanalysis of patients with PKD, the mean TC was 182+/-40mg/dl, LDL 101.2+/-33mg/dl, HDL 56.4+/-17mg/dl, and TG 123.7+/-59mg/dl. 76% of the PKD had GFR <60ml/min/1.73m² (N = 73), of which 43% presented LDL>100mg/dl (N = 32). In PKD patients with GFR > 60ml/min/1.73m² (N = 39), half (N = 22; 56.4%) also had LDL >100mg/dl. In addition, 51% were taking a statin, despite this they had a mean TC 183mg/dl+/-46, LDL 102.7+/-39, HDL 53+/-15, and TG 142+/-69mg/dl. Conclusion The presence of elevated LDL was frequent in CKD, especially in the group with GFR < 60ml/min/1.73m² without statin and in a quarter of patients with the same GFR with statin. It is notable in the PKD group, probably due to less awareness of strict CVR control.

#3521 ASSOCIATION BETWEEN NEPROLITHIASIS AND KIDNEY DISEASE PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENTS: A PROSPECTIVE COHORT STUDY

Abstract Background and Aims Nephrolithiasis is a common complication in Autosomal dominant polycystic kidney disease (ADPKD) patients and is known to occur in up to 8% to 36% of the patients. A few in vitro and in vivo studies showed that kidney and ureter stone formation could accelerate renal disease progression in ADPKD. However, its association between nephrolithiasis and renal function deterioration remains unknown in ADPKD patients. Methods This is a study from single center prospective cohort called HOPE-PKD. A total of 410 study subjects with abdominal computed tomography (CT) scan within 1 year before the enrollment were analyzed. Study subjects were divided into two groups according to the CT results as follows: Patients with papillary calcification, calyceal stone, ureter stone, or renal stone were classified as a stone group (n = 80, 19.5%), and patients only with renal cyst calcification or without any stones in the kidney and ureter were classified as a no-stone group (n = 330, 80.5%). The primary outcome was defined as the initiation of renal replacement therapy due to end-stage renal disease. The secondary outcome was a composite outcome of a 50% decline in estimated glomerular filtration rate (eGFR), doubling serum creatinine from baseline, or the initiation of renal replacement therapy. The hazard ratios (HRs) and 95% confidence interval (95% CI) for the outcome were analyzed using multivariate Cox regression analysis. Results There was no difference in the baseline characteristics between the stone group and the no-stone group. During a median 5.18 [interquartile range 3.41 - 8.03] year of follow-up, the primary and secondary outcomes occurred in 51 (12.4%) and 96 (23.4%) patients, respectively. In the unadjusted Cox regression analysis, there was no significant difference in the survival analysis between the two groups. However, after adjusting possible confounding factors (age, sex, body mass index, eGFR, comorbidity of hypertension and diabetes, serum uric acid, phosphorous and calcium level, results of PKD1 and PKD2 gene analysis, and Mayo classification), the stone group showed an increased risk of the primary and secondary outcome of HR 2.84 (95% CI 1.26 - 6.38; p-value 0.012) and HR 1.83 (95% CI 1.03 - 3.27; p-value 0.041), respectively compared to the no-stone group (Figure 1). Conclusion This is the first prospective cohort study showing that nephrolithiasis is associated with poor renal outcomes in patients with APDKD. Further clinical studies of nephrolithiasis in ADPKD patients are warranted to improve renal outcomes.

Parasympathetic activity and total fibrotic kidney in autosomal-dominant polycystic kidney disease patients: a pilot study

PurposeRenin–angiotensin system hyperactivation in autosomal-dominant polycystic kidney disease (ADPKD) patients leads to early hypertension. Cystic enlargement probably causes parenchymal hypoxia, renin secretion, and endothelial dysfunction. Sympathetic and parasympathetic balance is altered in this condition, especially during the night, also affecting blood pressure circadian rhythm. Aim of this study was to evaluate sympathetic/parasympathetic balance using heart rate variability (HRV) parameters and find a correlation between HRV and renal damage progression, as total kidney volume enlargement, in ADPKD patients.MethodsSixteen adult ADPKD patients were enrolled in the study. Eleven patients (68.8%) were male, and the median age was 42 years (IQR 36–47.5). HRV parameters were calculated using 24 h-ECG Holter. A kidney magnetic resonance imaging (MRI) scan 3 Tesla was performed to evaluate total kidney volume (TKV) and total fibrotic volume (TFV).ResultsA statistically significant positive linear correlation was observed between length of kidneys and frequency domain parameters as low frequency (LF) (r = 0.595, p < 0.05) and LFday (r = 0.587, p < 0.05). Moreover, a statistically significant positive linear correlation exists between high frequency (HF) and TFV (r = 0.804, p < 0.01) or height-adjusted (ha) TFV (r = 0.801, p < 0.01). Finally, we found a statistically significant positive linear correlation between HFnight and TKV (r = 0.608, p < 0.05), ha-TKV (r = 0.685, p < 0.01), TFV (r = 0.594, p < 0.05), and ha-TFV (r = 0.615, p < 0.05).ConclusionWe suppose that the increase in TKV and TFV could lead to a parasympathetic tone hyperactivation, probably in response to hypoxic stress and vasoconstriction due to cystic enlargement.

Identifying the main predictors of urine output in autosomal-dominant polycystic kidney disease (ADPKD) patients taking tolvaptan.

Few works have analyzed factors associated with urine output in ADPKD patients taking tolvaptan (TVP). We selected 24-h urine samples from ADPKD patients treated withTVP. Urine osmolality/creatinine ratio was used as estimator of urinary osmolar load. We included 127 urine samples from 61 patients. After TVP, urine output doubled with a parallel reduction in urine solute concentration. However, when expressed as urine solute/creatinine ratios, no significant changes were observed. Daily osmolar load and osmolality/creatinine ratio did not change significantly. Before TVP, urine output was positively correlated with body weight and urine osmolality/creatinine ratio and negatively with eGFR, urine morning osmolality, and 24-h urine-calculated osmolality. After TVP, urine output was positively correlated with body weight, eGFR and negatively with age. There was a poor correlation with urine-calculated osmolality. We constructed a predictor model using mixed-effects modeling and we found that urine output was related to lower age, higher body weight, higher eGFR, and greater doses of TVP. When body weight was removed, urine output was also related to male sex and a higher daily osmolar excretion. Equation of prediction was: Urine output (mL/day) = 2771-52.9 × Age (years) + 58.4 × Weight (kg) + 18.7 × eGFR (mL/min) + 870 (if TVP = 90/30mg) + 517 (if TVP = 60/30mg). Patients taking TVP will undergo an increase about twice in urine production from baseline. Greater doses of TVP cause a progressive increase in urine production. GFR, age, and body weight are the main predictors of future urine output in patients taking TVP.