Arterial Embolization of Polycystic Kidneys for Heterotopic Transplantation

Introduction: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization, performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an alternative to pretransplant nephrectomy. Materials and Methods: All patients who underwent pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction (OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day mortality and morbidity. Results: Thirty-one embolizations performed on 29 patients (medium age = 55.6; 62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases. Mean procedural time was 65 minutes (range = 35–106 minutes) and mean length of in-hospital stay was 3.8 days (range = 3–6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients (96.5%). The mean volume reduction was 39.9% (range = 6.01–68.2). The main observed complication was postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with a mean delay of 19.5 month (range = 4–54). Conclusion: Polycystic kidney embolization is an effective and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant recipients as an alternative to pretransplantation nephrectomy.

The Natural Course of Total Kidney Volume in Patients with Autosomal Dominant Polycystic Kidney Disease undergoing Hemodialysis

Objectives: The natural course of native kidneys after hemodialysis initiation in patients with autosomal dominant polycystic kidney disease (ADPKD) remains poorly understood.Methods: We measured the total volumes of native kidneys in 12 patients who had at least one enhanced computed tomography (CT) image both before and after initiation of hemodialysis (group 1) and in 18 patients who had no image before dialysis but more than two images after dialysis (group 2). In patients with images, the last image was used for analysis only after dialysis.Results: The mean total kidney volume (TKV) (± SD) before hemodialysis initiation was 3132 ± 1413 mL and the mean TKV of the last image was 3047 ± 1323 mL in group 1. The mean TKV change rate (%) was - 5.2 ± 27.4% (P > 0.05) during follow-up of 3.9 ± 1.9 years in group 1. The mean TKV change rate was 2.8 ± 34.4% (P > 0.05) in group 2. The follow-up period after dialysis initiation ranged from 4.2 ± 4.7 to 8.0 ± 5.2 years.Conclusions: The results suggest that the TKV of native polycystic kidneys decreases substantially after hemodialysis initiation. This reduction occurs mainly during the early post-hemodialysis period and followed by a slow enlargement of TKV.

Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD

Background and Objectives: Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. Design, Setting, Participants, and Measurements: In a randomized, placebo-controlled, double-blind trial, 68 children/ young adults 6-25 years of age with ADPKD and an estimated glomerular filtration rate >80 mL/min/1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight/day) or placebo, administered in powder form for 12 months. The co-primary outcomes were brachial artery flow-mediated dilation [FMDBA] and aortic pulse-wave velocity [aPWV]. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume]) by magnetic resonance imaging. In a sub-group of participants ≥18 years, vascular oxidative stress was measured as the change in FMDBA following an acute infusion of ascorbic acid. Results: Enrolled participants were 18±5 [mean±s.d.] years; 54% female; baseline FMDBA was 9.3±4.1 % change, and baseline aPWV was 512±94 cm/sec. Fifty-seven participants completed the trial. Neither co-primary endpoint changed with curcumin (estimated change [95% confidence interval] for FMDBA (% change): curcumin: 1.14 [-0.84, 3.13]; placebo: 0.33 [-1.34, 2.00]; estimated difference for change: 0.81 [-1.21, 2.84], p=0.48; aPWV (cm/sec: curcumin: 0.6 [-25.7, 26.9]; placebo: 6.5 [-20.4, 33.5]; estimated difference for change: -5.9 [-35.8, 24.0], p=0.67) (intent to treat). There was no curcumin-specific reduction in vascular oxidative stress, nor changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared to placebo. Conclusions: Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD.

Fetal Renal Volume and Fetal Renal Artery Doppler in Normal and Intrauterine Growth Restricted Fetuses

Background: Human fetal kidney undergoes constant changes throughout the pregnancy to attain final maturity in terms of structural and functional aspect. Approximately one million nephrons are seen on either side at birth in term fetuses. Many factors both maternal and fetal affect nephrogenesis viz. maternal malnutrition, maternal hyperglycemia, Intrauterine Growth Restriction (IUGR), vitamin A deficiency, and fetal exposure to some drugs. The aim of this study was to evaluate changes in the fetal renal artery Doppler parameter and fetal kidney volume measured by 3D ultrasound system with (VOCAL) method in normally grown and growth restricted fetuses after 26 weeks of gestation. Methods: This prospective study include 60 pregnant women divided in to two groups, first one (A) contains 30 pregnant women with intrauterine growth restricted fetuses, and the second one (B) contains 30 pregnant women with normally grown fetuses. Results: There was insignificant differences between two groups as regard gestational age by date but gestational age by US there was significant decrease in group A. There were insignificant differences between two groups as regard length of kidney either right or left. There was significant decrease in kidney width right and left side in group A versus group B. There was significant decrease in kidney depth right and left side in group A versus group B. There was significant decrease in kidney volume right and left side in group A versus group B. There was significant decrease in combined kidney volume in group A versus group B. There was significant increase in renal artery PI, RI in group A versus group B. Conclusions: Fetal hypoxemia which occurs in growth restricted fetuses leads to reduction in the percentage of the cardiac output reaching the kidneys which was reflected on Doppler as increase in the renal artery pulsatility index causing reduced renal perfusion. This reduction in the renal perfusion was responsible for impaired nephrogenesis and thus decreased kidney volume in growth restricted fetuses as compared to normal fetuses.

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) has phenotypic variability only partially explained by established biomarkers that do not readily assess pathologically important factors of inflammation and kidney fibrosis. We evaluated asymptomatic pyuria, a surrogate marker of inflammation, as a biomarker for disease progression. Methods: We performed a retrospective cohort study of adult patients with ADPKD. Patients were divided into asymptomatic pyuria (AP) and no pyuria (NP) groups. We evaluated the effect of pyuria on kidney function and kidney volume. Longitudinal models evaluating kidney function and kidney volume rate of change with respect to incidences of asymptomatic pyuria were created. Results: There were 687 included patients (347 AP, 340 NP). The AP group had more female (65.1% vs 49.4%). Median age at kidney failure was 86 and 80 years in NP and AP groups, respectively (Log-rank, p=0.49) for patients with Mayo Imaging Class (MIC)1A-1B as compared to 59 and 55 years for patients with MIC1C-1D-1E (Log-rank, p=0.02). Compared to NP group, the rate of kidney function (ml/min/1.73m2/year) decline shifted significantly after detection of asymptomatic pyuria in models including all patients (-1.48, p<0.001), MIC 1A-B patients (-1.79 , p<0.001), MIC 1C-1D-1E patients (-1.18, p<0.001), and PKD1 patients (-1.04, p<0.001). Models evaluating kidney volume rate of growth showed no change after incidence of asymptomatic pyuria as compared to NP group. Conclusions: Asymptomatic pyuria is associated with kidney failure and faster kidney function decline irrespective of the ADPKD gene, cystic burden, and cystic growth. These results support asymptomatic pyuria as an enriching prognostic biomarker for the rate of disease progression.-

Comparison of CT Volumetry versus Nuclear Renography for Predicting Remaining Kidney Function After Uninephrectomy in Living Kidney Donors

Computed tomography (CT) and nuclear renography are used to determine kidney procurement in living kidney donors (LKDs). The present study investigated which modality better predicts kidney function after donation. This study included 835 LKDs and they were divided into two subgroups based on whether the left-right dominance of kidney volume was concordant with kidney function (concordant group) or not (discordant group). The predictive value for post-donation kidney function between the two imaging modalities was compared at 1 month, 6 months, and > 1 year in total cohort, concordant, and discordant groups. Split kidney function (SKF) measured by both modalities showed significant correlation with each other at baseline. SKFs of remaining kidney measured using both modalities before donation showed significant correlation with eGFR (estimated glomerular filtration rate) after donation in the total cohort group and two subgroups, respectively. CT volumetry was superior to nuclear renography for predicting post-donation kidney function in the total cohort group and both subgroups. In the discordant subgroup, a higher tendency of kidney function recovery was observed when kidney procurement was determined based on CT volumetry. In conclusion, CT volumetry is preferred when determining procurement strategy especially when discordance is found between the two imaging modalities.

Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even observed a slight mean linear increase of 4.5 ml/m per year during childhood and adolescence for the overall cohort. Patients with two null PKHD1 variants had larger first documented haeTKV values than children with missense variants (median (IQR) haeTKV 793 (450–1098) ml/m in Null/null, 403 (260–538) ml/m in Null/mis, 230 (169–357) ml/m in Mis/mis). In the overall cohort, estimated glomerular filtration rate decreases with increasing haeTKV (median (IQR) haeTKV 210 (150–267) ml/m in CKD stage 1, 472 (266–880) ml/m in stage 5 without kidney replacement therapy). Strikingly, there is a clear correlation between haeTKV in the first eighteen months of life and kidney survival in childhood and adolescence with ten-year kidney survival rates ranging from 20% in patients of the highest to 94% in the lowest quartile. Early childhood haeTKV may become an easily obtainable prognostic marker of kidney disease in ARPKD, e.g. for the identification of patients for clinical studies.

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Introduction Diabetic nephropathy (DN), a global problem that threatens human health, is an important reason for chronic kidney disease and kidney failure. In our study, it was aimed to investigate the individual and combined effects of SA and EA in streptozotocin (STZ)-induced rats. Methods The groups are as follows: Control, untreated diabetic, diabetic treated with Sinapic acid (SA), diabetic treated with Ellagic acid (EA), diabetic treated with SA and EA, treated with SA, treated with EA, and treated with SA and EA. Total kidney volume, total glomerulus volume, total filtration space volume, caspase-3, and 8-OHdG immunoreactivity, Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), serum urea, and creatinine levels were evaluated by stereological, immunohistochemical, and biochemical methods. Results The findings of the study showed that total kidney volume, total glomerulus volume, total filtration gap volume, caspase-3, and 8-OHdG immunoreactivity, MDA, serum urea, and creatinine levels significantly increased in the untreated diabetic group compared to the control group. Also, severe mesangial and glomerular enlargement, extracellular matrix accumulation, and glomerular and tubular basal membrane thickness were observed in the tubulointerstitial and glomerular of the diabetic rats. However, individual and combined treatments of SA and EA ameliorated these histological changes. Additionally, decreased GSH and CAT in the untreated diabetic group increased by SA and EA treatment. Conclusions The findings suggest that treatment of SA and EA prevent apoptosis and DNA damage and structural changes in STZ-induced DN. However, the combined treatment of SA and EA were more effective than their individual treatments in all parameters except serum urea and creatinine.