Age- and height-adjusted total kidney volume growth rate in autosomal dominant polycystic kidney diseases.

BACKGROUND: The Mayo Clinic Image Classification (MIC) was proposed as a renal prognosis prediction model for autosomal dominant polycystic kidney disease (ADPKD). MIC is based on the assumption of exponential constant increase in height-adjusted total kidney volume (HtTKV). HtTKV growth rate is calculated by one-time measurement of HtTKV and age. We named it as an age-adjusted HtTKV growth rate (AHTKV-α). AHTKV-α was compared with HtTKV slope measured by at least two HtTKV values. METHODS: Comparison of repeatability between AHTKV-α and HtTKV slope, correlation of subgroups divided according to baseline AHTKV-α and HtTKV slope with disease manifestations, estimated glomerular filtration rate (eGFR) slope, and renal survival were analyzed in 296 patients with ADPKD. PKD genotype influences were compared between AHTKV-α and HtTKV slope in 88 patients with characterized PKD mutations. RESULTS: Absolute differences between baseline and follow-up measures were significantly larger for the HtTKV slope than for AHTKV-α (P < 0.0001). From baseline AHTKV-α-based subgroups A-E according to MIC, disease manifestations occurred earlier and future eGFR slopes became steeper (P < 0.0001). Multivariate hazard ratios of renal survival differed significantly among baseline AHTKV-α-based subgroups. Inter-subgroup differences in these predictors were less evident during baseline HtTKV slope-based classification. AHTKV-α values, but not HtTKV slopes, were significantly higher for PKD1 mutation carriers than for PKD2 mutation carriers (P < 0.0001). CONCLUSION: MIC is a good renal prediction model applicable to Japanese patients also. AHTKV-α can be a more sensitive and reliable indicator in TKV growth rate than HtTKV slope.

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

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

Safety study of somatostatin analogue octreotide for autosomal dominant polycystic kidney disease in Japan.

BACKGROUND: The total kidney volume (TKV) and total liver volume (TLV) increase and renal function decreases progressively in patients with autosomal dominant polycystic kidney disease (ADPKD). Somatostatin analogues, such as octreotide, reduce these increases in TKV and TLV. The aim of this study was to examine the safety of the short-term administration of octreotide long-acting release (octreotide-LAR) in a small number of cases. METHODS: Four ADPKD patients with an estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m(2), TKV > 1,000 mL, and TLV > 3,000 mL were enrolled. Two 20-mg octreotide-LAR intramuscular injections were repeated every 4 weeks for 24 weeks. Laboratory and clinical assessments were repeated every 4 weeks, and TKV and TLV were measured by magnetic resonance imaging before and after the study. RESULTS: In the laboratory tests, there was no abnormal variable except for a significant decrease of alanine aminotransferase. The means of TKV and TLV decreased from 2,007 to 1,903 mL and from 9,197 to 8,866 mL, respectively, but the changes were not significant. eGFR did not change significantly. Adverse events involved loose stools in two patients, as well as injection site granuloma and abdominal pain in one patient each, which resolved spontaneously. CONCLUSION: Octreotide-LAR may be safe and effective for preventing TKV and TLV increases (UMIN000009214).

Does increased water intake prevent disease progression in autosomal dominant polycystic kidney disease?

BACKGROUND: The clinical effects of increased water intake on autosomal dominant polycystic kidney disease (ADPKD) progression are unknown. METHODS: ADPKD patients with creatinine clearance ≧ 50 mL/min/1.73 m(2) were divided into high (H-, n = 18) and free (F-, n = 16) water-intake groups, mainly according to their preference. Prior to the study, 30 patients underwent annual evaluation of total kidney volume (TKV) and 24-h urine for an average of 33 months. During the 1-year study period, TKV and 24-h urine were analyzed at the beginning and end of the study and every 4 months, respectively. RESULTS: During the pre-study period, urine volume (UV) in the H-group was higher (P = 0.034), but TKV and kidney function and their slopes were not significantly different between the two groups. After the study commenced, UV further increased (P < 0.001) in the H-group but not in the F-group. During the study period, TKV and kidney function slopes were not significantly different between the two groups (primary endpoint). Plasma copeptin was lower (P = 0.024) in the H-group than in the F-group. TKV and kidney function slopes became worse (P = 0.047 and 0.011, respectively) after high water intake (H-group) but not in the F-group. High UV was associated with increased urine sodium, and urine sodium positively correlated with the % TKV slope (P = 0.014). CONCLUSIONS: Although the main endpoint was not significant, high water intake enhanced disease progression in the H-group when compared with the pre-study period. These findings necessitate a long-term randomized study before drawing a final conclusion.

Kidney volume and function in autosomal dominant polycystic kidney disease.

BACKGROUND: The significance of total kidney volume (TKV) as a biomarker of kidney function in autosomal dominant polycystic kidney disease (ADPKD) is controversial and has been reappraised. METHODS: Between 2007 and 2012, 64 patients were followed with a mean 39.7-month observation period. TKV measurements by magnetic resonance imaging and estimation of renal function with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and 24-h urine creatinine clearance were repeated annually. RESULTS: TKV and its adjusted parameters (height-adjusted, body surface area-adjusted and log-converted TKV [log-TKV]) correlated with eGFR significantly. Among them, the correlation coefficient of log-TKV was most significant (r = -0.6688, p < 0.001). The eGFR slope correlated negatively with TKV slope (p < 0.05). TKV increased faster and became larger as chronic kidney disease (CKD) stage advanced. As age advanced, eGFR declined significantly (p < 0.001), but the eGFR slope remained constant. There was no significant correlation between TKV and age, but the log-TKV slope became smaller as age advanced. If baseline TKV was large, the eGFR slope was steeper (p < 0.05), which suggests that eGFR declines faster in patients with larger kidney volume. CONCLUSIONS: TKV is confirmed as a clinically meaningful surrogate marker in ADPKD. Log-TKV correlates with eGFR most significantly. Higher rates of kidney enlargement and larger kidney volume are associated with a more rapid decrease in kidney function. Kidney function decreased faster as CKD stage advanced, but its declining slope did not change significantly by age, at least after ~30 years of age.

Comparison of effectiveness between modified transvaginal mesh surgery and vaginal pessary treatment in patients with symptomatic pelvic organ prolapse.

OBJECTIVES: This study aimed to compare the efficacy of modified transvaginal mesh (TVM) surgery and vaginal pessary in patients with symptomatic pelvic organ prolapse (POP). METHODS: We retrospectively analyzed 130 patients with symptomatic POP treated with either modified TVM (n = 62) or vaginal pessary (n = 68). To evaluate the prolapse, lower urinary tract, bowel, and sexual symptoms and prolapse-related quality of life (QOL) were assessed using the prolapse QOL questionnaire. All questionnaires were completed before treatment and 1 year after the treatment. RESULTS: One year after the treatment, the prolapse and voiding symptoms and all prolapse-related QOL domains, except for the personal relationships and sleep/energy, were significantly improved in the pessary group. The prolapse, urinary storage, voiding, bowel, and sexual symptoms and all QOL domains significantly improved in the modified-TVM group. CONCLUSIONS: Both the modified TVM surgery and vaginal pessary effectively treated prolapse and voiding symptoms and improved most of the prolapse-related QOL domains. Modified TVM surgery was more effective in improving urinary storage, bowel, and sexual symptoms than the pessary treatment. Modified TVM seemed to position the organs more correctly to improve bladder, bowel, and sexual function than pessary insertion.

[Comparison of clinical results between TUR-P and holmium laser enucleation of the prostate (HoLEP) based on the initial experience].

OBJECTIVE: We compared the surgical results between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TUR-P) for the treatment of men with benign prostatic hyperplasia (BPH). METHODS: A total of 87 patients with symptomatic BPH were analysed. HoLEP was performed on 46 men (mean age 68.2 +/- 7.5 years old) from December 2005 to February 2007, and TUR-P was performed on 41 men (mean age 69.2 +/- 7.3 years old) from April 2004 to March 2006. RESULTS: Both groups were comparable in terms of age, pre-operative IPSS, QOL index, urodynamic study results and prostate volume. During operation, decrease in hemoglobin was less in the HoLEP group than in the TUR-P group (1.15 +/- 1.2 vs 1.91 +/- 1.3 g/dl p < 0.05). The operation time was significantly longer in the HoLEP group than in the TUR-P group (161.9 +/- 65.0 vs. 118.3 +/- 36.9 minutes p < 0.001). Mean resected weight was 29.3 +/- 13.3 g (10-55) in the TUR-P group and 34.8 +/- 33.4 g (5-148) in the HoLEP group (p = 0.337). The catheterization period (52.1 +/- 29.6 vs. 115.2 +/- 27.5 hour p < 0.001) and hospital stay (6.6 +/- 2.3 vs. 9.4 +/- 2.2 days p < 0.001) were significantly shorter in the HoLEP group than in the TUR-P group. At follow up, Qmax, average flow rate and post void residual urine (PVR) in two groups improved significantly, and these parameters were not significantly different between the groups after 3 months. CONCLUSIONS: Both TUR-P and HoLEP were effective in relieving BOO. The estimated blood loss, a catheterization time and hospitalization were less or shorter in the HoLEP group. HoLEP may be a good alternative to the conventional transurethral electrocautery resection of the prostate for symptomatic BPH.

Kidney volume estimations with ellipsoid equations by magnetic resonance imaging in autosomal dominant polycystic kidney disease.

BACKGROUND: Kidney volume (KV) becomes clinically relevant in autosomal dominant polycystic kidney disease (ADPKD) management. KV can be conveniently estimated (ceKV) using ellipsoid volume equations with three axes measurements; however, the accuracy and reliability are unknown. METHODS: KVs of 347 kidneys in 177 consecutive ADPKD patients were determined with a volumetric method (standard-KV), and ceKV was calculated using six different ellipsoid equations with three axes measurements using magnetic resonance imaging. The inter- and intraobserver reliabilities were analyzed using intraclass correlation coefficients (ICCs). Ellipsoid-KVs were obtained by linear regression analysis between standard-KV and ceKVs, and six ellipsoid-KVs were validated with a bootstrap model. RESULTS: The ICCs of intra- and interobserver reliabilities in standard-KV and axes measurements were highly reliable. All ceKVs underestimated standard-KV and % differences between ceKV and standard-KV were reduced by ellipsoid-KVs. Bootstrap analyses suggested that six ellipsoid-KVs reliably simulated standard-KV. CONCLUSION: Among six ellipsoid-KVs, ellipsoid-KV3 = 84 + 1.01 x π/24 × Length × (sum of two width measurements)(2) relatively accurately simulated the standard-KV. Kidney volume estimation using ellipsoid equations is reliably applied to clinical management of ADPKD while recognizing wide scattering in the difference between estimated and volumetrically measured kidney volume.