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.

Improving the "second generation Daugirdas equation" to estimate Kt/V on the once-weekly haemodialysis schedule.

INTRODUCTION: The haemodialysis (HD) dose, as expressed by Kt/V urea, is currently routinely estimated with the second generation Daugirdas (D2) equation (Daugirdas in J Am Soc Nephrol 4:1205-1213, 1993). This equation, initially devised for a thrice-weekly schedule, was modified to be used for all dialysis schedules (Daugirdas et al. in Nephrol Dial Transplant 28:2156-2160, 2013), by adopting a variable factor that adjusts for the urea generation (GFAC) over the preceding inter-dialysis interval (PIDI, days). This factor was set at 0.008 for the mid-week session of the standard thrice-weekly HD schedule. In theory, by setting PIDI = 7, one could get GFAC = 0.0025, to be used in patients on the once-weekly (1HD/wk) schedule, but actually this has never been tested. Moreover, GFAC was derived not taking into account the residual kidney urea clearance (Kru). Aim of the present study was to provide a specific value of GFAC for patients on  a once-weekly hemodialysis schedule. SUBJECTS AND METHODS: The equation to predict GFAC (GFAC-1) in the 1HD/wk schedule was established in a group of 80 historical Italian patients (group 1) and validated in a group of 100 historical Spanish patients (group 2), by comparing the Kt/V computed using GFAC-1 (Kt/VGFAC-1) with the reference Kt/V (Kt/VSS) values, as computed with the web-based Solute-Solver software (SS) (Daugirdas et al. in Am J Kidney Dis 54:798-809, 2009). Three more sets of Kt/V (Kt/V0.008, Kt/V0.0025 and Kt/V0.0035) values were computed using the GFAC of the original D2 equation (0.008), the GFAC predicted by PIDI/7 (0.0025) and the mean observed GFAC-1 (0.0035), respectively. They were compared with the reference Kt/VSS values. RESULTS: The predicting equation obtained from group 1 was: GFAC-1 = 0.0022 + 0.0105 × Kru/V (R2 = 0.93). Mean Kt/VSS in the group 2 was 1.54 ± 0.29 SD (N = 500 HD sessions). The mean percent differences for Kt/V0.008, Kt/V0.0025, Kt/VGFAC-1, and Kt/V0.0035 were 5.1 ± 1.0%, - 1.4 ± 0.7%, 0.0 ± 0.3%, - 0.3 ± 0.7%, respectively. No statistically significant difference was found between Kt/V values, except for Kt/V0.008. CONCLUSION: A linear relationship was found between GFAC and Kru/V in patients on the 1HD/wk schedule. Such a relationship is able to improve the "second generation Daugirdas equation" for an accurate estimate of the single pool Kt/V in this setting. However, a simple replacement in the D2 equation of 0.008 with the mean observed GFAC (0.0035) could suffice in the clinical practice.

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.

What volume to choose to assess online Kt/V?

INTRODUCTION: Urea distribution volume (V) can be assessed in different ways, among them the anthropometric Watson Volume (VW). However, many studies have shown that VW does not coincide with V and that the latter can be more accurately estimated with other methods. The present multicentre study was designed to answer the question: what V to choose to assess online Kt/V? MATERIALS AND METHODS: Pre- and postdialysis blood urea nitrogen concentrations and the usual input data set for urea kinetic modelling were obtained for a single dialysis session in 201 Caucasian patients treated in 9 Italian dialysis units. Only dialysis machines measuring ionic dialysance (ID) were utilized. ID reflects very accurately the mean effective dialyser urea clearance (Kd). Six different V values were obtained: the first one was VW; the second one was computed from the equation established by the HEMO Study to predict the single pool-adjusted modelled V from VW (VH) (Daugirdas JT et al. KI 64: 1108, 2003); the others were estimated kinetically as: 1. V_ID, in which ID is direct input in the in the double pool variable volume (dpVV) calculation by means of the Solute-solver software; 2. V_Kd, in which the estimated Kd is direct input in the dpVV calculation by means of the Solute-solver software; 3. V_KTV, in which V is calculated by means of the second generation Daugirdas equation; 4. V_SPEEDY, in which ID is direct input in the dpVV calculation by means of the SPEEDY software able to provide results quite similar to those provided by Solute-solver. RESULTS: Mean± SD of the main data are reported: measured ID was 190.6 ± 29.6 mL/min, estimated Kd was 211.6 ± 29.0 mL/min. The relationship between paired data was poor (R2 = 0.34) and their difference at the Bland-Altman plot was large (21 ± 27 mL/min). VW was 35.3 ± 6.3 L, VH 29.5 ± 5.5, V_ID 28.99 ± 7.6 L, V_SPEEDY 29.4 ± 7.6 L, V_KTV 29.7 ± 7.0 L. The mean ratio VW/V_ID was 1.22, (i.e. VW overestimated V_ID by about 22%). The mean ratio VH/V_ID was 1.02 (i.e. VH overestimated V_ID by only 2%). The relationship between paired data of V_ID and VW was poor (R2 = 0.48) and their mean difference at the Bland-Altman plot was very large (- 6.39 ± 5.59 L). The relationship between paired data of V_ID and VH was poor (R2 = 47) and their mean difference was small but with a large SD (- 0.59 ± 5.53 L). The relationship between paired data of V_ID and V_SPEEDY was excellent (R2 = 0.993) and their mean difference at the Bland-Altman plot was very small (- 0.54 ± 0.64 L). The relationship between paired data of V_ID and V_KTV was excellent (R2 = 0.985) and their mean difference at the Bland-Altman plot was small (- 0.85 ± 1.06 L). CONCLUSIONS: V_ID can be considered the reference method to estimate the modelled V and then the first choice to assess Kt/V. V_SPEEDY is a valuable alternative to V_ID. V_KTV can be utilized in the daily practice, taking also into account its simple way of calculation. VW is not advisable because it leads to underestimation of Kt/V by about 20%.

[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.

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.