Revisiting nephrocalcinosis: A single-centre perspective. A northern Italian experience.

AIM: Nephrocalcinosis is a clinical-pathological entity characterized by the deposition of calcium salts within the kidney parenchyma. Both the protean presentation and multiple causes may explain the lack of data regarding its prevalence. The aim of this study is to report the prevalence and main clinical features of nephrocalcinosis diagnosed in a newly opened nephrology outpatient unit. METHODS: Analysis on the data we prospectively gathered from the start of activity (2007-2013) was carried out. Clinical and laboratory data were collected from the medical records and from the general laboratory; diagnosis was based upon imaging data reviewed by the same radiologists. RESULTS: Sixty-five of 2695 patients referred to our unit were diagnosed with nephrocalcinosis (2.4%). The affected patients were younger than the overall out-patient population (median: 37.7 (min-max: 8-82) vs 63 years (2-102) P < 0.001), with higher female prevalence (68% vs 51.4%: P < 0.05) and better preserved kidney function (CKD-EPI 103 (23-165) vs 60 mL/min (3.2-169) P < 0.001). Kidney stones were the main reason for referral (35.4%), followed by electrolyte disturbances (22.7%), acute pyelonephritis (4.6%), AKI or CKD (4.6%). Nephrocalcinosis was associated with autoimmune diseases in 29% and with microcythaemia in 23%, while positive family history was present in 23% of patients. Various electrolyte disturbances were observed, with hypercalciuria being the hallmark of beta thalassaemic patients. CONCLUSIONS: Nephrocalcinosis is a rare, but not exceptional disease in nephrology. In Mediterranean countries, microcythaemia would appear to be a major cause of this disease. Greater awareness of nephrocalcinosis is needed for an integrated approach involving various branches of internal medicine and radiology.

Diet as a system: an observational study investigating a multi-choice system of moderately restricted low-protein diets.

BACKGROUND: There is no single, gold-standard, low-protein diet (LPD) for CKD patients; the best compliance is probably obtained by personalization. This study tests the hypothesis that a multiple choice diet network allows patients to attain a good compliance level, and that, in an open-choice system, overall results are not dependent upon the specific diet, but upon the clinical characteristics of the patients. METHODS: Observational study: Three LPD options were offered to all patients with severe or rapidly progressive CKD: vegan diets supplemented with alpha-ketoacids and essential aminoacids; protein-free food in substitution of normal bread and pasta; other (traditional, vegan non supplemented and tailored). Dialysis-free follow-up and survival were analyzed by Kaplan Meier curves according to diet, comorbidity and age. Compliance and metabolic control were estimated in 147 subjects on diet at March 2015, with recent complete data, prescribed protein intake 0.6 g/Kg/day. Protein intake was assessed by Maroni Mitch formula. RESULTS: Four hundreds and forty nine patients followed a LPD in December, 2007- March, 2015 (90% moderately restricted LPDs, 0.6 g/Kg/day of protein, 10% at lower targets); age (median 70 (19-97)) and comorbidity (Charlson index: 7) characterized our population as being in line with the usual CKD European population. Median e-GFR at start of the diet was 20 mL/min, 33.2% of the patients were diabetics. Baseline data differ significantly across diets: protein-free schemas are preferred by older, high-comorbidity patients (median age 76 years, Charlson index 8, GFR 20.5 mL/min, Proteinuria: 0.3 g/day), supplemented vegan diets by younger patients with lower GFR and higher proteinuria (median age 65 years, Charlson index 6, GFR 18.9 mL/min; Proteinuria: 1.2 g/day); other diets are chosen by an intermediate population (median age 71 years, Charlson index 6; GFR 22.5 mL/min; Proteinuria: 0.9 g/day); (p <0.001 for age, Charlson index, proteinuria, GFR). Adherence was good, only 1.1% of the patients were lost to follow-up and protein intake was at target in most of the cases with no differences among LPDs (protein intake: 0.47 (0.26-0.86) g/Kg/day). After adjustment for confounders, and/or selection of similar populations, no difference in mortality or dialysis start was observed on the different LPDs. Below the threshold of e-GFR 15 mL/min, 50% of the patients remain dialysis free for at least two years. CONCLUSION: A multiple choice LPD system may allow reaching good adherence, without competition among diets, and with promising results in terms of dialysis-free follow-up. The advantages with respect to a non-customized approach deserve confirmation in further comparative studies or RCTs.

Moderate Protein Restriction in Advanced CKD: A Feasible Option in An Elderly, High-Comorbidity Population. A Stepwise Multiple-Choice System Approach.

BACKGROUND: Protein restriction may retard the need for renal replacement therapy; compliance is considered a barrier, especially in elderly patients. METHODS: A feasibility study was conducted in a newly organized unit for advanced kidney disease; three diet options were offered: normalization of protein intake (0.8 g/kg/day of protein); moderate protein restriction (0.6 g/kg/day of protein) with a "traditional" mixed protein diet or with a "plant-based" diet supplemented with ketoacids. Patients with protein energy wasting (PEW), short life expectancy or who refused were excluded. Compliance was estimated by Maroni-Mitch formula and food diary. RESULTS: In November 2017⁻July 2018, 131 patients started the program: median age 74 years (min⁻max 24-101), Charlson Index (CCI): 8 (min-max: 2⁻14); eGFR 24 mL/min (4⁻68); 50.4% were diabetic, BMI was ≥ 30 kg/m² in 40.4%. Normalization was the first step in 75 patients (57%, age 78 (24⁻101), CCI 8 (2⁻12), eGFR 24 mL/min (8⁻68)); moderately protein-restricted traditional diets were chosen by 24 (18%, age 74 (44⁻91), CCI 8 (4⁻14), eGFR 22 mL/min (5⁻40)), plant-based diets by 22 (17%, age 70 (34⁻89), CCI 6.5 (2⁻12), eGFR 15 mL/min (5⁻46)) (p < 0.001). Protein restriction was not undertaken in 10 patients with short life expectancy. In patients with ≥ 3 months of follow-up, median reduction of protein intake was from 1.2 to 0.8 g/kg/day (p < 0.001); nutritional parameters remained stable; albumin increased from 3.5 to 3.6 g/dL (p = 0.037); good compliance was found in 74%, regardless of diets. Over 1067 patient-months of follow-up, 9 patients died (CCI 10 (6⁻12)), 7 started dialysis (5 incremental). CONCLUSION: Protein restriction is feasible by an individualized, stepwise approach in an overall elderly, high-comorbidity population with a baseline high-protein diet and is compatible with stable nutritional status.

Patient Survival and Costs on Moderately Restricted Low-Protein Diets in Advanced CKD: Equivalent Survival at Lower Costs?

The indications for delaying the start of dialysis have revived interest in low-protein diets (LPDs). In this observational prospective study, we enrolled all patients with chronic kidney disease (CKD) who followed a moderately restricted LPD in 2007-2015 in a nephrology unit in Italy: 449 patients, 847 years of observation. At the start of the diet, the median glomerular filtration rate (GFR) was 20 mL/min, the median age was 70, the median Charlson Index was 7. Standardized mortality rates for the "on-diet" population were significantly lower than for patients on dialysis (United States Renal Data System (USRDS): 0.44 (0.36-0.54); Italian Dialysis Registry: 0.73 (0.59-0.88); French Dialysis Registry 0.70 (0.57-0.85)). Considering only the follow-up at low GFR (≤15 mL/min), survival remained significantly higher than in the USRDS, and was equivalent to the Italian and French registries, with an advantage in younger patients. Below the e-GFR of 15 mL/min, 50% of the patients reached a dialysis-free follow-up of ≥2 years; 25% have been dialysis-free for five years. Considering an average yearly cost of about 50,000 Euros for dialysis and 1200 Euros for the diet, and different hypotheses of "spared" dialysis years, treating 100 patients on a moderately restricted LPD would allow saving one to four million Euros. Therefore, our study suggests that in patients with advanced CKD, moderately restricted LPDs may allow prolonging dialysis-free follow-up with comparable survival to dialysis at a lower cost.

Low-Protein Diets in Diabetic Chronic Kidney Disease (CKD) Patients: Are They Feasible and Worth the Effort?

Low-protein diets (LPDs) are often considered as contraindicated in diabetic patients, and are seldom studied. The aim of this observational study was to provide new data on this issue. It involved 149 diabetic and 300 non-diabetic patients who followed a LPD, with a personalized approach aimed at moderate protein restriction (0.6 g/day). Survival analysis was performed according to Kaplan-Meier, and multivariate analysis with Cox model. Diabetic versus non-diabetic patients were of similar age (median 70 years) and creatinine levels at the start of the diet (2.78 mg/dL vs. 2.80 mg/dL). There was higher prevalence of nephrotic proteinuria in diabetic patients (27.52% vs. 13.67%, p = 0.002) as well as comorbidity (median Charlson index 8 vs. 6 p = 0.002). Patient survival was lower in diabetic patients, but differences levelled off considering only cases with Charlson index > 7, the only relevant covariate in Cox analysis. Dialysis-free survival was superimposable in the setting of good compliance (Mitch formula: 0.47 g/kg/day in both groups): about 50% of the cases remained dialysis-free 2 years after the first finding of e-GFR (estimated glomerular filtration rate) < 15 mL/min, and 1 year after reaching e-GFR < 10 mL/min. In patients with type 2 diabetes, higher proteinuria was associated with mortality and initiation of dialysis. In conclusion, moderately restricted LPDs allow similar results in diabetic and non non-diabetic patients with similar comorbidity.

Calcium-phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules.

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low-flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start-to-end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca-phosphate (P)-parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. "Severe" secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8-2.1 m(2) ), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca-P-PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start-to-end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in "severe" secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on "low-flow" daily home dialysis, in "severe" secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.

Which low-protein diet for which CKD patient? An observational, personalized approach.

OBJECTIVES: Low protein diets (LPDs) are milestones in chronic kidney disease (CKD). Concerns over compliance and safety limit their use. The aim of this study was to test the feasibility and main results of a multiple-choice approach to LPDs, adapted to patient preferences. METHODS: From December 2007 to January 2013, all CKD patients (stages 4/5; progressive stage 3) without contraindications (malnutrition, short life expectancy), were offered two main LPDs (proteins 0.6 g/kg daily): Vegan supplemented (LPD-KA) or with "aproteic" commercial food (LPD-ACF). LPDs followed a qualitative approach based on forbidden and allowed food; one to three free meals per week, and flexible control policy (1-3 mo). Start of dialysis, death, and combined outcome (death-dialysis) were analyzed by Kaplan-Meier curves and Cox model. Comparison with dialysis in patients with glomerular filtration rate (GRF) <15 mL/min, (corresponding to "early" dialysis start) employed standardized mortality rates, with respect to the Italian and the United States Dialysis Registry. RESULTS: One hundred eighty-five patients (222 patient-years) started at least a trial of LPD-KA, 122 (177 patients-years) LPD-ACF; only 3 patients with GFR <30 mL/min denied an LPD trial. Patients who chose LPD-KA were younger than those on LPD-ACF (63 versus 74 y), had less comorbidity (82% versus 93%), higher proteinuria (1.4 versus 0.7 g/d) and lower GFR (17 versus 23 mL/min) (P < 0.001). Median daily protein intake was 0.7 g/kg on both diets (Maroni-Mitch formula). The combined outcome (death or dialysis) was not influenced by the diet chosen (Cox analysis). Relative risk for death on the diet (patients with GFR <15 mL/min) was 0.5 with respect to the Italian Registry and 0.3 to the United States Dialysis Registry. The diets had comparable costs (1 y on dialysis: 50 patient-years on LPD). CONCLUSIONS: The choice of diet is strictly linked to patient characteristics, thus supporting a multiple-choice offer. Once corrected for baseline data, both LPDs led to similar results, suggesting at least survival equivalence with dialysis, at lesser cost.

Type 1 diabetes, diabetic nephropathy, and pregnancy: a systematic review and meta-study.

BACKGROUND: In the last decade, significant improvements have been achieved in maternal-fetal and diabetic care which make pregnancy possible in an increasing number of type 1 diabetic women with end-organ damage. Optimal counseling is important to make the advancements available to the relevant patients and to ensure the safety of mother and child. A systematic review will help to provide a survey of the available methods and to promote optimal counseling. OBJECTIVES: To review the literature on diabetic nephropathy and pregnancy in type 1 diabetes. METHODS: Medline, Embase, and the Cochrane Library were scanned in November 2012 (MESH, Emtree, and free terms on pregnancy and diabetic nephropathy). Studies were selected that report on pregnancy outcomes in type 1 diabetic patients with diabetic nephropathy in 1980-2012 (i.e. since the detection of microalbuminuria). Case reports with less than 5 cases and reports on kidney grafts were excluded. Paper selection and data extraction were performed in duplicate and matched for consistency. As the relevant reports were highly heterogeneous, we decided to perform a narrative review, with discussions oriented towards the period of publication. RESULTS: Of the 1058 references considered, 34 fulfilled the selection criteria, and one was added from reference lists. The number of cases considered in the reports, which generally involved single-center studies, ranged from 5 to 311. The following issues were significant: (i) the evidence is scattered over many reports of differing format and involving small series (only 2 included over 100 patients), (ii) definitions are non-homogeneous, (iii) risks for pregnancy-related adverse events are increased (preterm delivery, caesarean section, perinatal death, and stillbirth) and do not substantially change over time, except for stillbirth (from over 10% to about 5%), (iv) the increase in risks with nephropathy progression needs confirmation in large homogeneous series, (v) the newly reported increase in malformations in diabetic nephropathy underlines the need for further studies. CONCLUSIONS: The heterogeneous evidence from studies on diabetic nephropathy in pregnancy emphasizes the need for further perspective studies on this issue.