Biopsy-proven BK virus nephropathy in renal transplant recipients: A -multi-central study from Turkey (BK-TURK STUDY).

AIM: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. MATERIALS AND METHODS: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. RESULTS: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2 . In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. CONCLUSION: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Twelve to Twenty-year Follow-up of Dega Acetabuloplasty in Patients With Developmental Dysplasia of the Hip: Is it as Effective as Expected?

BACKGROUND: Although Dega acetabuloplasty is widely used for the treatment of developmental dysplasia of the hip, there is a paucity of data on long-term outcomes. The purpose of the study was to evaluate the rate of residual acetabular dysplasia after Dega acetabuloplasty. METHODS: Patients of a previously reported consecutive series of 35 patients (43 hips) operated by a single surgeon were recontacted for long-term follow-up. Of these, 25 patients (32 hips) consented, with a follow-up rate of 71% (74% of hips). The mean age at the time of surgery was 35 (18 to 65) months. The presence of residual dysplasia was noted according to the lateral center-edge angle of Wiberg, femoral head extrusion index, and Tönnis angle. The latest radiographic outcome was evaluated according to the Severin classification and patients were clinically evaluated according to the modified McKay criteria. RESULTS: The mean follow-up duration of 16.5 (12 to 20) years yielded an average age of 19.2 (14 to 23) years at the time of analysis. According to lateral center-edge angle, femoral head extrusion index, and Tönnis angle, 5 (15.6%) hips were dysplastic and 2 (6.3%) hips were reoperated for resubluxation. Thus, a total of 7 hips (21.9%) were considered to have residual dysplasia. With the exception of 2 hips that underwent further osteotomies, no other hips were re-subluxated or redislocated. Overcoverage was noted in 6 (18.7%) hips. There were 26 Severin group I and II (81.3%), 4 Severin group III (12.5%), and 2 Severin group IV (6.2%) hips. According to modified McKay criteria, 20 (62.5%) hips were excellent, 7 (21.9%) hips were good, and 5 (15.6%) were fair. Severin classification and modified McKay criteria were correlated with dysplasia ( P < 0.05). CONCLUSIONS: Seventy-eight percent of the hips treated by Dega acetabuloplasty for developmental dysplasia of the hip did not have acetabular dysplasia at a mean follow-up of 16 years. Even in well-treated asymptomatic hips, patients should be followed regularly, especially for residual dysplasia. LEVEL OF EVIDENCE: Level IV.

Acute kidney injury in Turkey: epidemiological characteristics, etiology, clinical course, and prognosis.

BACKGROUND: This study aimed to evaluate the etiologies, comorbidities, and outcomes of acute kidney injury (AKI) in Turkey and determine any potential differences among different geographical parts of the country. METHODS: This prospective observational study was conducted by the Acute Kidney Injury Working Group of the Turkish Society of Nephrology. Demographical and clinical data of patients with AKI at the time of diagnosis and at the 1st week and 1st, 3rd, and 6th months of diagnosis were evaluated to determine patient and renal survival and factors associated with patient prognosis. RESULTS: A total of 776 patients were included (54.7% male, median age: 67 years). Prerenal etiologies, including dehydration, heart failure, and sepsis, were more frequent than other etiologies. 58.9% of the patients had at least one renal etiology, with nephrotoxic agent exposure as the most common etiology. The etiologic factors were mostly similar throughout the country. 33.6% of the patients needed kidney replacement therapy. At the 6th month of diagnosis, 29.5% of the patients had complete recovery; 34.1% had partial recovery; 9.5% developed end-stage kidney disease; and 24.1% died. The mortality rate was higher in the patients from the Eastern Anatolian region; those admitted to the intensive care unit; those with prerenal, renal, and postrenal etiologies together, stage 3 AKI, sepsis, cirrhosis, heart failure, and malignancy; those who need kidney replacement therapy; and those without chronic kidney disease than in the other patients. CONCLUSION: Physicians managing patients with AKI should be alert against dehydration, heart failure, sepsis, and nephrotoxic agent exposure. Understanding the characteristics and outcomes of patients with AKI in their countries would help prevent AKI and improve treatment strategies.

Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. METHODS: This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. RESULTS: A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4-116.3), and median proteinuria was 6000 mg/d (IQR, 3656-9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. CONCLUSIONS: Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

Hypoxia-inducible factors in arteriovenous fistula maturation: A prospective cohort study.

BACKGROUND: Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia-inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end-stage kidney disease (ESKD) patients. METHODS: This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. Eight patients excluded from the study due to having unavailable veins six patients were excluded due to acute thrombosis after surgery. One patient lost to follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels were measured by the ELISA method. RESULTS: Compared with healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3 (1.0-1.9) vs 2.2 (1.6-3.0)] (P = .002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group (n = 19) and the failure group (n = 16). Serum HIF-2α level was 1.7 (1.1-1.8) in the mature group; however, it was 3.1 (2.8-3.3 in failure group (P < .001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α > 2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), P < .001]. CONCLUSIONS: HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.

A rare complication following internal jugular vein catheterization to malposition: acute Budd Chiari syndrome.

BACKGROUND: Tunneled catheters can be used as an alternative vascular access in patients with limited health expectancy,vascular access problems and several comorbidities. We aimed to present a patient with venous stenosis related- reversible acute Budd-Chiari syndrome after catheter malposition. CASE PRESENTATION: After changing of tunneled catheter insertion, 36-year old man was admitted to our hospital with sudden onset of nausea, fever, chills and worsening general condition In computed tomography (CT) imaging, a hypodense thrombus was observed in which the distal end of the catheter is at the level of drainage of the hepatic veins in the inferior vena cava and that blocked hepatic vein drainage around the catheter. The catheter was removed and a new catheter was inserted in the same session. Because patient's general condition was good and without fever, he was discharged with advices on the 9th day of hospitalization. CONCLUSION: Although catheter malposition and thrombosis are not a common complication, clinicians should be alert of these complications.

Effect of Systemic Oxytocin Administration on New Bone Formation and Distraction Rate in Rabbit Mandible.

PURPOSE: The main disadvantage of distraction osteogenesis is the prolonged treatment protocol. Recently, oxytocin (OT) has been found to have anabolic effects on bone metabolism. In this experimental study, the effects of OT on the mandibular distraction gap in rabbits at 2 different distraction rates were evaluated. MATERIALS AND METHODS: This experimental study was conducted on 28 male New Zealand white rabbits. The animals were divided into 3 experimental groups and 1 control group. Group A (control group, n = 7) consisted of animals with distraction at a rate of 1 mm/day, and group B (n = 7) consisted of animals with a distraction rate of 2 mm/day; groups A and B received postoperative saline solution injection. Group C (n = 7) consisted of animals with distraction at a rate of 1 mm/day, and group D (n = 7) consisted of animals with a distraction rate of 2 mm/day; postoperative OT injection was performed in groups C and D. RESULTS: Both histomorphologic and micro-computed tomography evaluations showed increased bone healing in the OT-treated groups. CONCLUSIONS: On the basis of the evaluation of both the histomorphometric and micro-computed tomographic data, systemic OT administration was found to increase new bone formation and bone healing with distraction osteogenesis.

Autosomal dominant polycystic kidney disease: new role for ultrasound.

OBJECTIVES: To evaluate the accuracy of US in calculating renal volumes and renal resistive index (RRI) that was obtained using a new method in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: In this prospective study, US and MRI were performed in 57 patients with ADPKD (31 female and 26 male; age range, 19-79 years) between August 2017 and May 2018. The volumes determined using US and MRI were compared. The ellipsoid formula was re-evaluated using different multipliers. RRI was obtained 1.5-2 cm distal to the outlet of main renal arteries. The relationship between mean RRI, renal function tests, and kidney volumes and difference between mean RRI of ADPKD patients with and without renal failure were investigated using a two-sided independent samples t test and Pearson correlation test. Interobserver agreements for volume assessments and RRI measurements were determined. RESULTS: By changing the ellipsoid formula, a very good agreement was found (ICC 0.970 for the right kidney and ICC 0.973 for the left kidney). The mean RRI in the right renal artery was 0.61 ± 0.07 and in the left renal artery 0.63 ± 0.06. The mean RRI of ADPKD patients with renal failure was significantly higher than that of patients without renal failure (p = 0.005). There was a significant correlation between mean RRI and renal function tests. CONCLUSION: The accuracy of the US in calculating renal volumes increases by adapting the ellipsoid formula. RRI may be used for the management of ADPKD independently of volumes. KEY POINTS: •The accuracy of ultrasonography for renal volume measurement increases by changing the classical ellipsoid formula. •Renal resistive index measured by color Doppler ultrasonography is helpful for the management of autosomal dominant polycystic kidney disease. •The role of Doppler US in autosomal dominant polycystic kidney disease should increase as a result of our findings.

Multiple urinary tract infections are associated with genotype and phenotype in adult polycystic kidney disease.

BACKGROUND: Urinary tract infections (UTI) are one of the important clinical presentations in patients with autosomal dominant polycystic kidney disease (ADPKD). The association between UTI among genotypic and phonotypic properties of ADPKD patients is still obscure. Thus, we investigated the relationship between UTI and polycystin gene mutation with total kidney volume. METHODS: Forty patients with ADPKD patients with a history of more than two UTI and age-gender-matched 40 ADPKD patients without UTI history enrolled in the study. Ambulatory blood pressure monitoring was performed in all participants. Magnetic resonance imaging (MRI) was performed with a 1.5-T system, and total kidney volumes were calculated using mid-slice technique. To determine PKD1 and PKD2 genotype, we performed molecular and genetic tests involving the following steps: DNA isolation, next-generation sequencing (NGS) and data analysis. RESULTS: ADPKD patients with UTI had lower eGFR values than those without UTI [64.9 (32.2-100.8) vs 89.5 (59.0-110.0) (p = 0.041)]. In addition, patients with UTI had significantly increased height-adjusted total kidney volume than patients without UTI [950 (290-1350) vs 345 (243-780.0) (p = 0.005)]. Multiple logistic regression analysis showed that the PKD1-truncating mutation and hTKV independently predicted UTI. The sensitivity and specificity of hTKV were 65% and 77% (cutoff > 727 cm3) with an area of under the ROC curve of 0.70 (95% CI 0.56-0.85, p = 005). CONCLUSIONS: ADPKD patients with larger kidneys and PKD1 mutation are susceptible to increased risk of multiple UTI. Additionally, renal function decreased in ADPKD patients with multiple UTI history.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease.

BACKGROUND: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. METHODS: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1ß, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. RESULTS: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1ß (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035). CONCLUSIONS: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

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.

Role of vascular calcification inhibitors in preventing vascular dysfunction and mortality in hemodialysis patients.

Cardiovascular events make up the primary cause of death in hemodialysis patients, and the risk for cardiovascular mortality is significantly increased by vascular calcification, a condition observed frequently in this patient population. The mechanisms underlying the pathogenesis of vascular calcification are complex, and many factors facilitate or hinder the development of calcification. In this review, we first summarize the main factors contributing to the pathogenesis of vascular calcification in patients with end-stage renal disease. We then explore the role of calcification inhibitors in the calcification process, as well as their effect on vascular dysfunction and mortality in hemodialysis patients.

Oral rehabilitation with implant-supported fixed dental prostheses of a patient with cleidocranial dysplasia.

This clinical report describes the oral rehabilitation with implant-supported fixed dental prostheses in the maxilla and mandible of a patient with cleidocranial dysplasia. Cone-beam computed tomography and a tilted implant protocol in the mandible helped to establish a conservative approach for bone preservation, prevent surgical complications, enable proper implant positioning to avoid anatomic structures, and support the fixed dental prostheses.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

Hormonal changes in hemodialysis patients: Novel risk factors for mortality?

Patients with end-stage renal disease undergoing dialysis commonly experience derangements in the hypothalamic-pituitary-gonadal axis together with alterations at the level of synthesis and clearance of many hormones. This hormonal imbalance, even if asymptomatic, has recently been associated with increased mortality in these patients. In this review, we summarize observational and mechanistic evidence linking hormonal alterations at the level of the thyroid and sex-hormone systems with this mortality risks.

Serum micro-rna profiles in patients with autosomal dominant polycystic kidney disease according to hypertension and renal function.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder with unclear disease mechanism. Currently, overt hypertension and increased renal volume are the best predictors of renal function. In this study, we assessed the usefulness of selected circulating microRNAs (miRs) to predict disease progress in a cohort with ADPKD. METHODS: Eighty ADPKD patients (44.6 ± 12.7 years, 40% female, 65% hypertensive) and 50 healthy subjects (HS; 45.4 ± 12.7, 44% female) were enrolled in the study. Serum levels of 384 miRs were determined by Biomark Real Time PCR. Groups were compared using the limma method with multiple-testing correction as proposed by Smyth (corrected p < 0.01 considered significant). RESULTS: Comparing ADPKD to HS, we found significant differences in blood levels of 18 miRs (3 more and 15 less abundant). Of these, miR-3907, miR-92a-3p, miR-25-3p and miR-21-5p all rose while miR-1587 and miR-3911 decreased as renal function declined in both cross-sectional and longitudinal analysis. Using ROC analysis, an increased baseline miR-3907 in the circulation predicted a > 10% loss of GFR over the following 12 months (cut-off >2.2 AU, sensitivity 83%, specificity 78%, area 0.872 [95% CI: 0.790-0.953, p < 0.001]). Adjusting for age and starting CKD stage using multiple binary logistic regression analysis did not abrogate the predictive value. CONCLUSION: Increased copy numbers of miR-3907 in the circulation may predict ADPKD progression and suggest pathophysiological pathways worthy of further study.

Effects of Local Low-Dose Alendronate Injections Into the Distraction Gap on New Bone Formation and Distraction Rate on Distraction Osteogenesis.

Bisphosphonates that constrain bone resorption have a direct effect on osteoclast function. In this experimental study, the effects of low-dose local alendronate injections on the distraction gap (DG) in rabbit mandible at 2 different rates were evaluated.The experimental study was conducted on 20 male, New Zealand white rabbits. The animals were divided into 3 experimental groups and 1 control group. Group 1 consisted of animals with distraction at the rate of 1 mm/day, receiving postoperative local low-dose alendronate local injections into the DG. Group 2 consisted of animals with distraction at the rate of 2 mm/day, receiving postoperative 0.75 µg/kg of alendronate local injections into the DG. Group 3 consisted of animals with distraction at the rate of 2 mm/day, receiving postoperative 0.2 mL local saline injections into the DG. Group 4 consisted of animals with distraction at the rate of 1 mm/day, receiving postoperative 0.2 mL local saline injections into the DG. All the injections were performed immediately postoperatively and for all groups at 1, 2, 3, and 4 weeks following surgery. The distraction zones were evaluated using dual-energy X-ray absorptiometry and histological analysis.Histologically, bone healing was found to be significantly accelerated in Groups 1 and 4 compared with Groups 2 and 3 (P < 0.05). Bone healing was superior in Group 1 and the difference was statistically significant compared with Group 4. There was a significant increase in mean bone mineral density in the 1 mm daily rate groups (Groups 1 and 4) compared with the 2 mm daily rate groups (Groups 2 and 3) (P < 0.05).Local low-dose alendronate injections could be an effective way for improving bone formation in distraction osteogenesis. Furthermore, the results of this study did not support the hypothesis that injections of local low-dose alendronate may allow 2 mm/day instead of 1 mm/day of elongation in the rabbit mandible.

Stress Analysis of Zygomatic Implants on the Augmented Maxillary Sinus: Is It Necessary to Graft?

PURPOSE: Zygomatic implants are becoming an ideal therapy with advanced implant-supported prosthetic treatment for the posterior atrophic maxilla. The purpose of this study is to examine the quantity and distribution of stress, which was caused by zygomatic implants placed using intrasinus method with or without augmentation to the atrophic posterior maxilla. MATERIALS & METHODS: In this study, 3-dimensional atrophic edentulous maxilla models with and without sinus augmentation are designed with computer-aided programs. Stress analysis was carried out on the created computer models for maxillary alveolar cortical bone, for cortical bone in the zygomaticomaxillary suture, and for zygomatic spongy bone at the apex of the zygomatic implant and for metal substructure of Von Misses stress data. RESULTS: Having augmented the maxillary sinus with graft, it was observed that after the loading especially in the posterior region, the tensile and compressive stresses on the alveolar crest was distributed more homogeneously and the stress generated on the cortical bone was reduced through the graft. CONCLUSION: Although zygomatic implants are graftless solutions for athrophic maxilla, sinus augmentation will be useful for bearing stress around the implants.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. RESULTS: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. CONCLUSIONS: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease.

BACKGROUND: In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease. METHODS: We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up. RESULTS: At baseline, median eGFR was 69 mL/min./1.73 m2, mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44-75) mL/min./1.73 m2, 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p < 0.001), ΔFMD (0.599, p < 0.001), ΔcIMT (0.562, p < 0.001) and ΔPWV (0.27, p < 0.001) also after linear regression modeling to correct for confounders. Finally, ROC analysis was done for a high baseline copeptin with ΔeGFR [cut-off:≤59], ΔFMD [cut-off: ≤7.08], ΔcIMT [cut-off:>0.76], and ΔPWV [cut-off:≤7.80]. CONCLUSIONS: Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.