Glycemic pattern in diabetic patients on hemodialysis: continuous glucose monitoring (CGM) analysis.

BACKGROUND/AIMS: Recent evidences suggest that hemodialysis (HD) induces glycemic variations in diabetic patients. Continuous glucose monitoring (CGM) devices measure interstitial glucose in a 'Holter-like' manner thereby improving the glycemic control assessment method. METHODS: A CGM device (Medtronic iPRO) was used on 12 diabetic patients with chronic HD for 6 days to assess intra- and extra-dialytic interstitial glucose. RESULTS: In all enrolled patients, HD was associated with a decrease of interstitial glucose values. Intradialytic glucose nadir was 79 mg/dl and it was reached at the third hour after the beginning of the session. At the end of HD, interstitial glucose increased in all patients and a glycemic peak (187 mg/dl) occurred after an average time of 2.5 h. No episodes of nocturnal hypoglycemia occurred. CONCLUSION: HD is associated with significant intradialytic reduction of glycemia and postdialytic hyperglycemia. CGM devices result in better monitoring of glycemic trends in diabetic patients on chronic HD and could improve insulin management.

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

A single cystatin C determination before coronary angiography can predict short and long-term adverse events.

BACKGROUND: Cystatin C (CyC) role in the detection of contrast induced acute kidney injury (CIAKI) is controversial. This study assessed whether a single CyC determination before coronary angiography (CA)could predict CIAKI and long-term adverse events. METHODS: CyC was assessed before CA in 713 consecutive patients. CIAKI was the primary endpoint, defined as ≥0.3 mg/dl creatinine (sCR) increase at 48 h or ≥50% in 7-days. All-cause death, cardiovascular (CV)death and MACE (acute coronary syndrome, acute pulmonary edema,CV death) were secondary endpoints. Re-hospitalization, in-hospital death and worsening renal function were tertiary endpoints. RESULTS: CIAKI occurred in 47 (6.7%) patients. ROC analysis showed a good accuracy of CyC in the prediction of CIAKI (AUC 0.82,p < 0.01), compared with baseline sCR and sCR-eGFR (AUC 0.70 and 0.75 respectively, both p < 0.01). CyC was associated with 10-year CV-death, all-cause death and MACEs (AUC 0.76,0.74 and 0.64 respectively,all p < 0.01). A CyC cut-off value of 1.4 mg/L was not only accurate in predicting or ruling-out CIAKI following CA (97% negative predictive value, 84% specificity), but also useful as a prognostic marker for 10-year adverse events (50% vs.16% all cause mortality, 29% vs.3% CV death, 39% vs.13% MACE,all p < 0.01), re-hospitalizations (54% vs.35%,p < 0.01) and worsening renal function (34% vs.19%,p < 0.01). The strongest and independent risk factor for 10-year CV death was baseline CyC>1.4 mg/L (HR 17.3, 95% CI 1.94-155.1). CONCLUSIONS: A baseline determination of CyC before CA can accurately rule out CIAKI and predict adverse events in the long term. CIAKI can be ruled out before CA in 97% patients with a CyC value < 1.4 mg/L.

Urinalysis: do not forget this type of cell in renal transplantation.

Microscopic sediment analysis of urine from a 56-year-old woman who underwent renal transplantation showed many uncommon clusters of rounded and translucent cells containing globular mucous cytoplasmic inclusions (HPF, x400). These cells were bigger than leukocytes and, compared with uroepithelial cells, showed a smaller nucleus to cytoplasm ratio and appeared eosinophilic, being pink rather than azurophilic with Sternheimer-Malbin stain. They were also unlikely to be tubular cells, which are usually smaller, singly distributed and associated with dysmorphic erythrocytes and/or casts and/or a worsening in renal function. A review of the patient's history showed that a pretransplantation urologic surgical treatment, including ileal bladder reconstruction, had been performed. Intestinal epithelial cells should be remembered when examining urinary sediment.

Subcapsular Hematoma Causing Anuria After Renal Graft Trauma.

A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.

Dialysis choice in the context of an early referral policy: there is room for self care.

BACKGROUND: Predialysis care is vital for the patient and is crucial for dialysis choice: empowered, early referred patients tend to prefer out-of-hospital and self-care treatment; despite these claims, early referral remains too often a program more than a reality. Aim of the study was to evaluate the pattern and reasons for RRT choice in patients treated in a long-standing outpatient network, presently following 850 chronic patients (about 80% diabetics), working with an early referral policy and offering a wide set of dialysis options (home hemo and PD; self care and limited care hemodialysis; hospital hemodialysis). METHODS: Prospective historical study. All patients who started RRT in January 2001-December 2003 were considered. Correlations between demographical (sex, age, educational level) or clinical variables (pre-RRT follow-up, comorbidity, SGA and Karnofsky) and treatment choice have been tested by univariate (chi-square, Kruskal-Wallis) and multivariate models (logistic regression), both considering all choices and dichotomising choice into "hospital" versus "out of hospital dialysis". RESULTS: Hospital dialysis was chosen by 32.6% of patients; out of hospital in 67.4% (PD 26.5%, limited-care 18.4%, home hemodialysis 4.1%, self-care 18.4%). Hospital dialysis and PD were chosen by elderly patients (median age: 67.5 and 70 years respectively) with multiple comorbidities (75% and 92.3%); no difference for age, comorbidity, Karnofsky, SGA and educational level. 6/13 PD patients needed the help of a partner. Self-care/home hemodialysis patients were younger (median age 52), had higher educational level (p = 0.014) and lower prevalence of comorbidity (63.6% vs 94.7% in the other dialysis patients, p = 0.006). In the context of a long follow-up period (3.9 years) a statistically significant difference was found comparing hospital dialysis (3.3 years) vs out of hospital dialysis (4.9 years) (p = 0.035). In a logistic regression model, only pre-RRT follow-up was correlated with dialysis "hospital vs "out of hospital" choice (p = 0.014). CONCLUSION: Early nephrological follow-up may enhance self and home-based dialysis care.

Neutrophil Gelatinase Associated Lipocalin Is an Early and Accurate Biomarker of Graft Function and Tissue Regeneration in Kidney Transplantation from Extended Criteria Donors.

BACKGROUND: Delayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD. METHODS: We evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction. RESULTS: Plasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio). CONCLUSIONS: NGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.

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.

Continuum of therapy in progressive renal diseases (from predialysis to transplantation): analysis of a new organizational model.

In the aging of Western populations, decreased mortality is counterbalanced by an increase in morbidity, particularly involving chronic diseases such as most renal diseases. The price of the successful care of chronic conditions, such as cardiovascular diseases or diabetes, is a continuous increase in new dialysis patients. However, the increased survival of patients on chronic renal replacement therapies poses new challenges to nephrologists and calls for new models of care. Since its split from internal medicine, nephrology has seen a progressive trend toward super specialization and the differentiation into at least 3 major branches (nephrology, dialysis, and transplantation), following a path common to several other fields of internal medicine. The success in the care of chronic patients is owed not only to a careful technical prescription, but also to the ability to teach self-care and attain compliance; this requires good medical practice and a sound patient-physician relationship. In this context, the usual models of care may fail to provide adequate coordination and, despite valuable single elements, could end up as an orchestra without a conductor. We propose an integrated model of care oriented to the type of patient (tested in our area especially for diabetic patients): the patient is followed-up by the same team from the first signs of renal disease to eventual dialysis or transplantation. This model offers an interesting alternative both for patients, who usually seek continuity of care, and for nephrologists who prefer a holistic and integrated patient-physician approach.

Flexibility as an implementation strategy for a daily dialysis program.

BACKGROUND: Daily hemodialysis (DHD) is an interesting dialysis option, experienced worldwide by only a few hundred patients, because of clinical and logistic limitations. This study describes the main clinical and implementation results of a flexible policy applied in starting a DHD program. METHODS: The setting is the University Nephrology Center of Turin, Italy (approximately 150 hemodialysis and 50 peritoneal dialysis (PD) patients) where in November 1998 a short daily DHD program was started. Outcome measures were logistical (enrollment rate, indications and drop-outs) and clinical (dialysis efficiency, metabolic control, hypertension and anemia control). RESULTS: 25 patients experienced DHD, 16 (11% of the hemodialysis pool) were on DHD in November 2001; overall the DHD follow-up was 409.1 months (median 18, range 0.7-36 months). Flexibility was applied to schedules (patients modulated dialysis time and could switch to 3-4 sessions/wk); treatment setting (home: 11 patients, limited care center: 13; alternate settings: one); clinical selection (23/25 patients with comorbidity). Main reasons for choice were poor tolerance of previous schedule and the search for "best" treatment. Five patients dropped out (work reasons), one died on DHD and three were grafted. As compared to baseline, dialysis efficiency increased (EKRc pre-DHD 14.5 +/- 2.1 mL/min; 17.4 +/- 2.8 mL/min and 17.7 +/- 3.5 mL/min at 1-6 months; p<0.000). Despite the potentially confusing effect of comorbidity, the main clinical data improved. CONCLUSIONS: A flexible approach allowed development of DHD in approximately 11% of hemodialysis patients, with promising clinical results, despite frequent comorbidity.

Kidney rupture: an unusual and oligosymptomatic complication in a dialysis patient with acquired cystic disease.

Acquired cystic kidney disease (ACKD) is a complication of end-stage renal disease, the prevalence of which is related to dialysis duration; incidence of ACKD and associated conditions (neoplasia, hemorrhage) have decreased with improvements in renal transplantation and with the ageing of the dialysis population. This report regards spontaneous kidney rupture in a 57-year old patient, on home hemodialysis for 11 years, with ACKD for 5 years. At the end of a dialysis session, the patient reported sudden onset of colicky flank pain, followed by macrohematuria. Pain remitted with low doses of pain relievers, leaving dull flank discomfort. The patient self diagnosed a renal colic, and called the hospital two days later. At referral, two large hemorrhagic renal masses (7 and 2.8 cm) were found at ultrasound and CT scan. At surgery, kidney rupture was diagnosed. This case highlights the life threatening complications associated with ACKD, and underlines that massive renal hemorrhage may occur with relatively minor symptoms.

Biochemical and microscopic urinalysis: time and cost in a nephrology laboratory.

BACKGROUND: Urinalysis is a fundamental test in internal medicine and nephrology. Figures for costs are available in the general laboratory, where biochemical and microscopic urinalysis are commonly performed as semiautomated screening tests. Information on costs is lacking in the nephrology laboratory, where a time-consuming morphological analysis is usually preferred. This study analyses the costs of urinalysis in a nephrology laboratory. METHODS: In the nephrology laboratory at the University of Turin - Italy, biochemical urinalysis consists of multi-property strip and proteinuria/creatininuria, done by laboratory technicians. Phase-contrast microscopy is done by a nephrologist or biologist. Time dedicated to the tests was recorded by the same operator over 20 working days, during which 350 urine samples were processed (median 19/day, range 842). The production costs were calculated with the logic bottom-up technique. RESULTS: Overall time needed was 11.9 minutes/sample. Biochemical urinalysis required 6.6 minutes/sample; time required and samples processed were inversely related (< or =19 samples: 7.95 minutes/sample; >19 samples: 5.6 minutes/sample, p=0.01). Microscopic urinalysis took 5.3 minutes/slide; the best time-to-samples ratio was at 18-22 samples per day (with peak efficiency at 21 samples: 4.6 minutes). Cost of reagents and disposables was Euro1.06/sample. Time accounted for euro 5.32/sample (technicians, nephrologist-biologist), with total direct cost of euro 6.38/sample. CONCLUSION: In a nephrology laboratory, microscopic urinalysis is a time-consuming, expensive test. Analysis of cost and modalities may be useful, in a time of budget constrains, to maintain a role for this precious semeiotic art.

Referral of type 1 diabetic patients to a nephrology unit: will pre-emptive transplantation change our life?

BACKGROUND: Type 1 diabetic patients are a small but challenging subset of chronic kidney disease. The new frontiers of pancreas-kidney transplantation may enhance the need for early referral. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a specialized Nephrology Unit, and to quantify the indications for pancreas or pre-emptive pancreas-kidney transplantation at referral in this population. PATIENTS AND METHODS: Setting of study was a Nephrology Outpatient Unit, dedicated to diabetics, active since 1986; period of study 1991--2002. The main biochemical and clinical parameters were analyzed at referral. Indications for transplantation were put at: serum creatinine (sCr)> or =2 mg/dL or > or =3 mg/dL and/or nephrotic syndrome. Pancreas: lesser degrees of functional impairment without worsening after FK-506 challenge. RESULTS: 90 type 1 diabetics were referred: 48 males, 42 females; median age: 38 (18-65) years; median diabetological follow-up 20 (3-37) years; sCr 1.2 (0.6-7) mg/dL, proteinuria 0.9 (0-12.3) g/day; creatinine clearance: 58 (6-234) ml/min; Hbalc: 8.8% (5.9-14), diastolic blood pressure: 80 (55-100) mmHg, systolic blood pressure: 137.5 (70-180) mmHg. 85.6% had signs of end-organ damage due to diabetes. 67% of the patients had diabetic nephropathy, 20.7% hypertensive with or without diabetic nephropathy. According to the chosen criteria, 30.6% had indications for pancreas-kidney graft (sCr > or = 2 mg/dL), 25.9% considering sCr > or = 3 mg/dL; 28.2% further patients could be considered for isolated pancreas graft. CONCLUSIONS: At referral to the nephrologist, over 50% of type 1 diabetics may have indications for pancreas-kidney or pancreas graft; an earlier multidisciplinary work-up is needed to optimize an early pre-emptive transplant approach.

Teenagers' point of view on living donor kidney transplantation: Cinderella or princess?

UNLABELLED: Living kidney donation is an important clinical option, encountering different fortunes in the world. AIM: To analyse the opinions of a large subset of older teenagers attending high school (7999 students, median age 18) on different aspects of living kidney transplantation. METHODS: Analysis of semistructured questionnaires submitted within an educational campaign on dialysis and transplantation in the high schools of Torino and its county (about 2,000,000 inhabitants). RESULTS: Over 90% of the students had already heard of transplantation, mainly via television (88.4% county, 84.5% city). 80% would donate a kidney to a family member (3.5% wouldn't, 16.5% uncertain); answers were correlated with sex (females more than males p<0.0001), school type (istituti tecnici versus licei p=0.007), interest (yes versus other p<0.0001). A lower percent of individuals would receive a kidney (58.4% county, 59.4% city), only 10% would ask for donation. Over 40% of students consider legally buying a kidney a patient's right, only 26.6% would discourage this choice. The answers were correlated with the reverse pattern as for non-mercenary donation with type of school (licei more than istituti tecnici: p<0.0001), sex (males versus females p<0.0001), interest (not versus yes: p=0.002). CONCLUSIONS: Teenagers are favourable towards all forms of living kidney donation. The lower prevalence of positive answers on acceptance versus donation suggests that fears of endangering the donor's health may be one of the causes for a low living donation rate in our setting. The mixed answers on mercenary donation suggest discussing this complex issue in future educational programs.

Early referral of Type 2 diabetic patients: are we ready for the assault?

BACKGROUND: Elderly diabetics on dialysis are dramatically increasing in number. Their late referral reduces efficacy of therapeutic interventions; early referral is fundamental for their survival on dialysis. However, need for nephrological follow-up in case of early referral is not assessed. The objective was to define the need for follow-up in the nephrology setting of Type 2 diabetics, according to the early referral criteria of serum creatinine > or = 1.5 mg/dl or macroproteinuria. METHODS: The setting of the study was an outpatient diabetic care unit (University of Torino), where approximately 25% of the Type 2 diabetics of a 900,000-inhabitant city (Torino, Northern Italy) were followed. At the time of the study (1998-1999) the unit followed 5182 Type 2 diabetics whose serum creatinine and proteinuria were tested at least yearly. A total of 3826 prevalent and 478 incident patients with one or more analyses in the same laboratory were included in the study. Demographic data were not statistically different between selected and excluded patients. We calculated the stepwise need for nephrological follow-ups calculated according to our usual policy (4-12 evaluations/ year, on serum creatinine and proteinuria, and 30 min/evaluation). RESULTS: The prevalence of increased serum creatinine and macroproteinuria was high (in the prevalent cohort: serum creatinine > or = 1.5 mg/dl, 8.1%; proteinuria 0.3 g/day, 25.2%; serum creatinine > or = 3 mg/dl, 1.2%; nephrotic proteinuria 3.4%). Projecting data to the entire unit, with adherence to our evaluation protocol, early nephrological follow-up of Type 2 diabetics requires approximately 1300 h/year (one full-time nephrologist); five nephrologists are needed for our city, and 24 for the region (4350 000 inhabitants). CONCLUSIONS: Early nephrological referral and follow-up of Type 2 diabetics is time consuming and expensive. Meeting the outpatient care needs of this critical cohort requires considerable resources.

Why Our Patients Like Daily Hemodialysis.

The option of daily hemodialysis (HD) was discussed in November 1998 with a group of 35 HD patients on home or self-care/limited-care HD in a single, freestanding unit. After the meeting, 3 patients on home HD chose to switch to daily HD. The clinical success of the first patient and the immediate followers was one of the main reasons for further extension of this experience. At the time of this writing (February 2000), 10 patients were on a daily HD program (8 at home and 2 in a self-care/limited-care center) and one was in training for home daily HD. One further patient who tried 1 month of daily HD dropped out for logistic reasons. On daily HD, patients are dialyzed 2 - 3 hours/day, 6 days/ week, with blood flow of 270 - 300 mL/min, on bicarbonate dialysate with individually determined levels of Na and K. The schedule is flexible and a switch to 3 - 4 dialyses/week is occasionally allowed for working needs or for vacation. In addition to the well-known clinical advantages (better well-being, blood pressure control, nutrition, etc.), some patients preferred daily HD because of easier organization of daily activities, including work schedule. Patients initially feared frequent needle punctures and excessive burden on partners, but those concerns proved to be less a problem than anticipated. All current patients are willing to continue daily HD; only a nursing shortage limits further extension of the program in the self-care/limited-care center.