Could incremental haemodialysis be a new standard of care? A suggestion from a long-term observational study.

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years. Subjects and methods: The dataset of all patients starting HD between January 1st, 2000 and December 31st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment. Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.

The lacking equation that estimates the protein catabolic rate in patients on once-weekly haemodialysis.

BACKGROUND: The normalized protein catabolic rate (PCRn) is one of the key indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. Ideally, it should be assessed using the double pool UKM (KDOQI clinical practice guidelines, AIKD, 2015), as the web-based software Solute-Solver (SS) does (Daugirdas et al., AJKD, 2009). Simple formulae exist to compute PCRn for patients on thrice- or twice-weekly HD schedule, but not for patients on once-weekly HD schedule (1HD/wk). Aim of the present technical note was to introduce the lacking equation that estimates PCRn in the 1HD/wk regimen. METHODS: Data of a single HD session associated to monthly UKM studies were retrieved from the electronic database of our dialysis unit for 80 historical patients on 1HD/wk regimen. The UKM parameters, as calculated with SS, were used in a subgroup of 40 randomly selected patients (group 1) to build-up a multiple regression model of PCRn. The latter was used to predict PCRn (PCRnPred) values in the cohort of the remaining 40 patients (group 2). The Bland-Altman plot was used to analyse the agreement between PCRnPred and the paired "observed" (PCRnObs) values, as measured with SS. RESULTS: The following equation was established by means of the multiple regression analysis: PCRn = - 0.46 + 0.01 × C0 + 0.09 × eKt/V + 3.94 × Kru/V, where C0 is pre-dialysis blood urea nitrogen concentration, eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. The PCRnPred values were 0.99 ± 0.24 g/kg/day; the PCRnObs values were 0.96 ± 0.23 g/kg/day (mean difference 0.03 ± 0.05 g/kg/day). Their difference at the Bland-Altman analysis ranged from - 0.08 to + 0.13 g/kg/day. Finally, a nomogram was drawn: it can be used to estimate not only PCRn from Kru/V and C0, but also C0 as a function of Kru/V and PCRn. CONCLUSIONS: The equation here introduced allows a simple and accurate estimate of PCRn in patients on once-weekly HD regimen. The availability of the nomogram relating C0 to PCRn and Kru/V could be a further step to make safer and safer the once-weekly HD regimen. The following equation was established by means of the multiple regression analysis [Formula: see text] where PCRn is the normalized protein catabolic rate (PCRn), C0 is pre-dialysis blood urea nitrogen concentration (BUN), eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. A nomogram relating pre-dialysis BUN to PCRn and Kru/V could be drawn: it can be used to estimate not only PCRn from Kru/V and pre-dialysis BUN, but also pre-dialysis BUN as a function of Kru/V and PCRn.

[Identification of a new mutation of the NPHP1 gene].

Kidney cystic diseases are inherited disorders causing chronic renal failure. According to the genetic defect they are classified as diseases of the primary ciliary complex and uromodulin-associated diseases. Mutations in genes coding for ciliary proteins are the basis of a broad category of genetic diseases, called ciliopathies. To date, three important ciliopathies are known: the autosomal dominant form and the recessive shape of the polycystic kidney and the nephronophthisis (NPHP). Juvenile Nephronophthisis (NPHP) is a progressive renal tubulo-interstitial disorder with a form of autosomal recessive inheritance that progresses inexorably towards terminal renal failure. Three different forms have been distinguished: juvenile (NPH1), infantile (NPH2) and adolescent (NPH3). Juvenile Nephronophthisis or nephronophthisis type 1 (NPH1), is the most frequent form. In most patients with a suspected diagnosis of NPHP, based primarily on clinical and radiological data, the deletion in homozygous NPHP1 is present in 20-40% of cases. Heterozygous deletions are found in 6% of patients, with concomitant mutation of the NPHP1 gene on the second allele. In this study we subjected to genetic screening 6 patients with suspected NPHP causing chronic renal failure, belonging to 6 families. The genetic screening identified in 2/6 patients a deletion of exons 5-7-20 and in 4/6 patients an heterozygous deletion of exon 20 and an heterozygous deletion on exon 17 not yet described in literature. Our results suggest that genetic screening should be included in the diagnostic procedure of patients with suspected nephronophthisis and that it may be used alternatively to renal biopsy.

LDL-apheresis accelerates the recovery of nonarteritic acute anterior ischemic optic neuropathy.

Nonarteritic acute anterior ischemic optic neuropathy (NAION) is a disabling disease which impairs visual function. It is presumed to result from disturbances of microcirculation in the anterior portion of the optic nerve head due to hemodynamic factors derived from excessive blood viscosity, or restriction of the vasal lumen in hypertensive, hypercholesterolemic, diabetic patients. We aimed to determine whether acute reduction of plasma fibrinogen and serum low-density lipoprotein (LDL) cholesterol is effective for treatment of NAION. We recruited 11 patients (7 females, 4 males) with a mean age of 57.2 +/- 19.6 years. All except one of them presented risk factors for atherosclerosis. The mean values of LDL-cholesterol and fibrinogen before treatment were 144 +/- 32 mg/dL and 341 +/- 80 mg/dL, respectively. All were treated with standard therapy (prednisone, salicylate, pentoxiphyllin) and underwent three sessions of LDL-apheresis (HELP system-B Braun) that can reduce plasma LDL-cholesterol and fibrinogen by more than 50% in a very short time. In all patients we observed a drastic reduction of LDL cholesterol and fibrinogen and a clear improvement in the visual functional data. In fact, mean values of corrected vision increased from 3.7/10 +/- 3/10 to 7.9/10 +/- 2.2/10 (P = 0.002) after the third session, while the scotomatous portion of the visual field regressed after the first session, and in 5 patients further regressed after the third session. This improvement had remained stable after 3 months. Thanks to it's effect of antagonizing hemorheologic disorders of the ocular microcirculation, fibrinogen/LDL-apheresis seems to be an efficacious treatment of NAION.

Renal vascular resistance and renin-angiotensin system in the pathogenesis of early hypertension in autosomal dominant polycystic kidney disease.

Activation of the renin-angiotensin system (RAS) has been proposed to increase renal vascular resistance (RVR) and to play a role in the development of hypertension in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to investigate the relationship among RVR, RAS and blood pressure (BP) profile in patients without renal impairment. Thirty-four ADPKD patients underwent ambulatory blood pressure monitoring (ABPM) over a 24-h period and were divided into two groups: 17 hypertensive (group A, day-systolic BP > or = 135 mmHg and/or day-diastolic BP > or = 85 mmHg) and 17 normotensive (group B, day-BP < 135/85 mmHg) patients. The two groups were comparable with respect to age, sex, and renal function. None of the patients assumed therapy. In all subjects the plasma renin activity (PRA) was measured, and the RVR was assessed by measuring resistivity indices (RI). RI was significantly higher in the hypertensive than in normotensive patients (0.67 +/- 0.05 vs. 0.62 +/- 0.03), while PRA was normal in all subjects, and showed no statistical difference between the two groups. Taking all the patients together (group A + group B), a significant positive correlation between RI and 24-h mean arterial pressure (MAP) was discovered, but no correlation was found between RI and PRA or between MAP and PRA. We conclude that in ADPKD patients without renal impairment the MAP values are strictly correlated with the RVR, but not with PRA. Thus factors other than RAS probably contribute to the increase of the RVR and to the early development of hypertension.

Altered p53 and pRb expression is predictive of response to BCG treatment in T1G3 bladder cancer.

BACKGROUND: The aim of this study was to determine the prognostic value of p53 and retinoblastoma protein (pRb) expression in patients with stage T1 grade 3 (T1G3) bladder cancer (BC) treated by transurethral resection of bladder tumour (TURBT) and intravesical instillations of bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: p53 and pRb expression were independently recorded within a homogeneous series of 27 patients. Fisher exact test and the log-rank test were carried out, along with Kaplan-Meier survival analysis. RESULTS: Sixteen tumours showed altered p53 expression, while 14 showed altered pRb expression. Overall, 7 tumours showed normal expression of both markers, 10 altered expression of one of the two markers, and 10 altered expression of both markers. Only altered pRb expression was an independent predictor of both recurrence (p=0.037) and progression (p=0.018); altered expression of both markers was a strong predictor (p=0.001) of progression. CONCLUSION: This is the first study demonstrating that altered p53 and pRb expression are predictive of T1G3 BC response to BCG treatment. These findings provide grounds for inclusion and prospective validation of these markers in the decision-making process for treating BC.

Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS: We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS: Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS: Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.