Elisabetta Mezza

Comparison between 24‐h proteinuria, urinary protein/creatinine ratio and dipstick test in patients with nephropathy: Patterns of proteinuria in dipstick‐negative patients

Objective. Three main tests are commonly employed for the measurement of proteinuria: the dipstick test, the urinary protein/creatinine ratio (P/C) and the 24‐h urine collection. The aim of this study was to evaluate the correlation between these methods, comparing linear regression and ROC curve data. Material and methods. A total of 297 consecutive outpatients with different renal diseases were included in the study. Twenty‐four‐hour proteinuria was considered the reference test. Results. A high degree of correlation was observed between all the tests (p<0.0001), the highest regression coefficient being between 24‐h proteinuria and P/C (R = 0.82), and the lowest between P/C and the dipstick test (R = 0.72). The dipstick test failed to detect pathological proteinuria in 94 patients (31.6 %). Therefore, in these subjects, the patterns of proteinuria were assessed by immunofixation and sodium dodecyl sulphate (SDS) electrophoresis. Conclusions. Our data strongly support the use of urinary P/C for the detection of proteinuria, at least in nephrology units, where the prevalence of proteinuria is likely to be high.

Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study

Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis.

Low-protein vegetarian diet with alpha-chetoanalogues prior to pre-emptive pancreas-kidney transplantation.

BACKGROUND Pre-emptive pancreas-kidney transplantation is increasingly considered the best therapy for irreversible chronic kidney disease (CKD) in type 1 diabetics. However, the best approach in the wait for transplantation has not yet been defined. AIM To evaluate our experience with a low-protein (0.6 g/kg/day) vegetarian diet supplemented with alpha-chetoanalogues in type 1 diabetic patients in the wait for pancreas-kidney transplantation. METHODS Prospective study. Information on the progression of renal disease, compliance, metabolic control, reasons for choice and for drop-out were recorded prospectively; the data for the subset of patients who underwent the diet while awaiting a pancreas-kidney graft are analysed in this report. RESULTS From November 1998 to April 2004, 9 type 1 diabetic patients, wait-listed or performing tests for wait-listing for pancreas-kidney transplantation, started the diet. All of them were followed by nephrologists and diabetologists, in the context of integrated care. There were 4 males and 5 females; median age 38 years (range 27.9-45.5); median diabetes duration 23.8 years (range 16.6-33.1), 8/9 with widespread organ damage; median creatinine at the start of the diet: 3.2 mg/dl (1.2-7.2); 4 patients followed the diet to transplantation, 2 are presently on the diet, 2 dropped out and started dialysis after a few months, 1 started dialysis (rescue treatment). The nutritional status remained stable, glycemia control improved in 4 patients in the short term and in 2 in the long term, no hyperkalemia, acidosis or other relevant side effect was recorded. Proteinuria decreased in 5 cases, in 3 from the nephrotic range. Albumin levels remained stable; the progression rate was a loss of 0.47 ml/min of creatinine clearance per month (ranging from an increase of 0.06 to a decrease of 2.4 ml/min) during the diet period (estimated by the Cockroft-Gault formula). CONCLUSIONS Low-protein supplemented vegetarian diets may be a useful tool to slow CKD progression whilst awaiting pancreas-kidney transplantation.

Cholesterol crystal embolism syndrome in dialysis patients: an emerging clinical diagnosis?

Background: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. Methods: The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. Results: Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200–210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47–70) and end-stage renal disease follow-up 11.5 years (3–25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, ‘conventional’ hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). Conclusion: The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).

The grafted kidney takes over: disappearance of the nephrotic syndrome after preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.

Daily dialysis Kt/V and flexible schedules: is it possible to control efficiency, when and how?

Background Daily hemodialysis is a promising treatment schedule but uniform criteria for defining efficiency are lacking. Methods On our daily dialysis (DD) schedule, duration is flexible (2–3 hours, patients are free to add up to 30min/session), Qb 250–350 mL/min; dialyser 1.6–1.8 m2. Study was performed on 12 pts on DD for ≥2 months, with ≥4 Kt/V on subsequent days, tested in the same laboratory. Goal: To evaluate variability and identify a simple method for weekly calculation, Kt/V was assessed for 133 sessions. Results On flexible DD, variability of Kt/V-session is high (relative error 4.9%-22%). On flexible schedules, within the time range chosen (2–3 hours) variability of average hourly Kt/V is lower (standard deviation: min (0.014; max (0.052 hour, relative error 4.9%-10%) allowing calculation of weekly Kt/V (averaging 3 sessions: relative error <6%) suitable for clinical practice. Conclusions Flexible schedules, allowing patients to increase treatment time, are an interesting clinical option, but a challenge for Kt/V assessment.

A Simple Method for the Classification of Proteinuria

We read with interest the paper of Bergon et al. about the classification of renal proteinuria (1) and we agree with the authors that in the presence of proteinuria or diagnosed nephropathy it is indispensable to measure protein excretion rate in a 24-hour urine collection using a dye-binding assay with pyrogallol-red (2, 3). Otherwise, in our experience a correct evaluation of proteinuria typing is a correct and feasible method that leads to a better standardization of the results. Furthermore, the assessment in mid-stream morning second urine samples by a nephelometric analysis of urinary proteins, using urinary protein/creatinine ratios allows a reduction of pre-analytical errors linked to urine time collection and to possible protein digestion by proteases action in 24-hour-stored urine (4). Recent studies shed new light into the physiopathlogical mechanisms of urinary protein excretion: thus, in our opinion a correct method of classification of proteinuria must distinguish not only between glomerular and tubular proteinuria but, in a better way, between selective glomerular proteinuria (presence of albumin and transferrin) and not selective glomerular proteinuria (presence of proteins with MW >100 kDa), and also between incomplete tubular proteinuria (presence of proteins with MW <50 kDa) and complete tubular proteinuria (presence of proteins with MW <23 kDa) (5). Data obtained showed that complete tubular proteinuria was an index of stronger tubular pathological involvement often associated to higher levels of serum creatinine and to a worse outcome (6). In our laboratory we developed an immunofixation method using specific polyclonal antisera, for qualitative/semi-quantitative analysis of urinary proteins (retinol-binding protein: RBP; α1-microglobulin: α1m; albumin; transferrin; immunoglobulin G: IgG and α2-macroglobulin: α2m), allowing a better definition of selectivity of glomerular proteinuria and of complete or incomplete tubular proteinuria (CSI-Nefro Cinque, BIOCI, Turin, Italy) (7). The CSI (Cross Star Immunofixation) method is a gel-immunoprecipitation, characterized by a high analytical sensitivity. This is due to the characteristics of the gel itself, to the mono-specificity of the antisera and to the new type of cross-deposition of the samples and

‘Bench’ MRI before transplant on harvested kidneys: a possible tool for diagnosis of acute pyelonephritis

We present the first case in which magnetic resonance imaging (MRI) has been utilized to rule out lesions compatible with acute pyelonephritis in kidneys from a cadaveric organ donor before transplanting them. A 40-year-old female underwent diagnosis of brain death following a septic shock. The ecotomography of the kidneys showed areas compatible with micro-abscesses raising the hypothesis of acute pyelonephritis. Our radiologist proposed to perform a bench-MRI (maintaining kidneys within the sterile preservation bags constantly on ice); this did not show lesions except little cysts not relevant by the clinical point of view. We transplanted kidneys without infective complications and results were very good.

CKD patients and erythropoietin: do we need evidence-based informed consent?

Background Consent to therapy is increasingly requested in the form of “informed consent”. Objective To validate an evidence-based informed consent form for erythropoietin (EPO) therapy and to evaluate patient opinions about the informed consent approach. Methods An evidence-based informed consent form was developed as part of the Evidence-Based-Medicine course at the Medical School of Turin, Italy. It was validated by anonymous questionnaires (0–10 analogical scales and open answers) administered to patients at different stages of CKD (19 pre-ESRD, 26 hemodialysis, 12 transplant patients) attending an outpatient unit of the University of Turin, to 8 nurses, and to 26 medical students. Results All individuals filled in the questionnaire. Interest in a detailed explanation of the therapy was high (median 9), as was comprehension (median 9), with no differences between patients with regard to disease stage (pre-ESRD vs. RRT) or educational level. Prior knowledge of the therapy was affected by the educational level (p=0.013 for the advantages and p=0.004 for the side effects) and the professional role (patients vs caregivers: p=0.009 for the advantages and p<0.001 for side affects); patient knowledge of the advantages (median 6) tended to increase as the disease progressed (p=0.015). The most common response by patients was that informed consent was necessary for all drugs (35.1%); 73.1% of the caregivers considered it necessary only for severe side effects. The preferred modality of consent was discussion with the caregiver during the clinical controls (42% of all cases). Conclusions Patient interest in and comprehension of an informed consent form with a detailed explanation of the therapy was high; the caregivers opinion was still the most valued teaching tool.