A cross-sectional study on the relationship between hematological data and quantitative morphological indices from kidney biopsies in different glomerular diseases.

BACKGROUND: The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e.g. fractal analysis) with clinical and hematological parameters using a cross-sectional design. METHODS: Whole slide images from sixty-seven biopsies of patients diagnosed for diabetic nephropathy, hypertensive nephropathy, focal segmental glomerulosclerosis (FSGS) or IgA nephropathy have been used. The images have been semi-automatically quantified in the ImageJ environment, in order to derive the glomerular density, the tubular density, the number of tubules per glomerulus and the fractal dimension of the tubular lumen in the cortex (an index of complexity of the tubular lumen). For each patient, hemato-chemical data have been retrieved, including the uric acid level and the creatinine-based eGFR. RESULTS: A linear relationship between eGFR and glomerular density was observed in hypertension and FSGS, but not in diabetic nephropathy. Conversely, the eGFR correlated with the tubular density across different glomerular conditions. Moreover, the tubular density was linearly correlated with uric acid levels in different pathological conditions. The fractal dimension of tubular lumen was correlated with the eGFR but only in hypertensive patients. Finally, blood pressure was not correlated to any of the morphological indices tested. CONCLUSIONS: We propose the use of the fractal dimension as a new morphological descriptor of the nephron integrity.

Quality of Life in CKD Patients on Low-Protein Diets in a Multiple-Choice Diet System. Comparison between a French and an Italian Experience.

Prescribing a low-protein diet (LPD) is part of the standard management of patients in advanced stages of chronic kidney disease (CKD). However, studies on the quality of life (QoL) of patients on LPDs are lacking, and the impact these diets have on their QoL is often given as a reason for not prescribing one. We, therefore, decided to assess the QoL in a cohort of CKD stage 3-5 patients followed up by a multiple-choice diet approach in an outpatient nephrology clinic in France. To do so, we used the short version of the World Health Organization's quality of life questionnaire and compared the results with a historical cohort of Italian patients. We enrolled 153 patients, managed with tailored protein restriction in Le Mans, and compared them with 128 patients on similar diets who had been followed in Turin (Italy). We found there were no significant differences in terms of age (median 73 vs. 74 years, respectively), gender, CKD stage, and comorbidities (Charlson's Comorbidity Index 7 vs. 6). French patients displayed a greater body mass index (29.0 vs. 25.4, p < 0.001) and prevalence of obesity (41.2 vs. 15.0%, p < 0.001). Baseline protein intake was over the target in France (1.2 g/kg of real body weight/day). In both cohorts, the burden of comorbidities was associated with poorer physical health perception while kidney function was inversely correlated to satisfaction with social life, independently of the type of diet. Our study suggests that the type of LPD they follow does not influence QoL in CKD patients and that a personalized approach towards protein restriction is feasible, even in elderly patients.

Ready to Change: Attitudes of an Elderly CKD Stage 3-5 Population towards Testing Protein-Free Food.

The recent Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines suggest an early start of protein restriction, raising issues on willingness to change dietary habits. The aim of this exploratory real-life study was to report on a test of dietary products (protein-free, not previously available in France) in a large, mainly elderly, chronic kidney disease (CKD) population (220 patients, median age: 77.5 years, Charlson comorbidity index (CCI): seven, malnutrition inflammation score (MIS): five, estimated glomerular filtration rate (eGFR): 26 mL/min), also as a means to tailor further implementation strategies. Forty-nine patients (22.28%) were considered to be poor candidates for the trial (metabolically unstable or with psychological, psychiatric or logistic barriers); of the remaining 171, 80.70% agreed to participate. Patients to whom the diet was not proposed had lower eGFR and higher comorbidity (eGFR 21 vs. 27 p = 0.021; MIS six vs. four p: <0.001). Patients who refused were 10 years older than those who accepted (83 vs. 73 years p < 0.001), with a higher CCI (eight vs. seven p = 0.008) and MIS (five vs. four p = 0.01). In the logistic regression, only age was significantly associated with refusal to participate (Odds ratio (OR): 5.408; 95% CI: 1.894 to 15.447). No difference was found according to low/intermediate/high frequency of weekly use of protein-free food. Our study suggests that most of the patients are ready to test new diet approaches. Only old age correlated with refusal, but frequency of implementation depended on individual preferences, underlying the importance of tailored approaches to improve adherence.

New Intravenous Calcimimetic Agents: New Options, New Problems. An Example on How Clinical, Economical and Ethical Considerations Affect Choice of Treatment.

BACKGROUND: Dialysis treatment is improving, but several long-term problems remain unsolved, including metabolic bone disease linked to chronic kidney disease (CKD-MBD). The availability of new, efficacious but expensive drugs (intravenous calcimimetic agents) poses ethical problems, especially in the setting of budget limitations. METHODS: Reasons of choice, side effects, biochemical trends were discussed in a cohort of 15 patients (13% of the dialysis population) who stared treatment with intravenous calcimimetics in a single center. All patients had previously been treated with oral calcimimetic agents; dialysis efficacy was at target in 14/15; hemodiafiltration was employed in 10/15. Median Charlson Comorbidity Index was 8. The indications were discussed according to the principlist ethics (beneficience, non maleficience, justice and autonomy). Biochemical results were analyzed to support the clinical-ethical choices. RESULTS: In the context of a strict clinical and biochemical surveillance, the lack of side effects ensured "non-maleficence"; efficacy was at least similar to oral calcimimetic agents, but tolerance was better. Autonomy was respected through a shared decision-making model; all patients appreciated the reduction of the drug burden, and most acknowledged better control of their biochemical data. The ethical conflict resides in the balance between the clinical "beneficience, non-maleficience" advantage and "justice" (economic impact of treatment, potentially in attrition with other resources, since the drug is expensive and included in the dialysis bundle). The dilemma is more relevant when a patient's life expectancy is short (economic impact without clear clinical advantages), or when non-compliance is an issue (unclear advantage if the whole treatment is not correctly taken). CONCLUSIONS: In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice. While ethical discussions are not aimed at finding "the right answer" but asking "the right questions", this example can raise awareness of the importance of including an ethical analysis in the choice of "economically relevant" drugs.