Multiple, random spot urine sampling for estimating urinary sodium excretion.

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%.Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection.

Fenoldopam and renal hemodynamics in shiga toxin-related hemolytic uremic syndrome.

BACKGROUND: Fenoldopam, a vasodilating agent, may represent a potential therapeutic opportunity to increase renal perfusion in those conditions where renal hemodynamics are severely impaired by vascular sub-occlusion, as, indeed, is the case in thrombotic microangiopathies. METHODS: The renal resistance index (RRI) was measured, on and off fenoldopam, in 27 children with STEC-HUS. RESULTS: A 12% decrease in RRI was observed on fenoldopam compared to off treatment without changes in the systemic hemodynamics and with no side effects. CONCLUSIONS: If confirmed in larger series, fenoldopam may become an important addition to supportive care to reduce ischemic damage in STEC-HUS and improve long-term outcomes.

Kidney transplant in patients with atypical hemolytic uremic syndrome in the anti-C5 era: single-center experience with tailored Eculizumab.

RATIONALE AND OBJECTIVE: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. STUDY DESIGN: This is a single center case series presenting our experience with KTx in aHUS. SETTING AND PARTICIPANTS: This study included 26 patients (16 females) with a diagnosis of aHUS, who spent a median of 5.5 years on kidney replacement therapy before undergoing KTx. We compared the aHUS relapse rate in three groups of patients who underwent KTx: patients who received no prophylaxis, patients who underwent plasma exchange, those who received Eculizumab prophylaxis. Complement factor H-related disease was by far the most frequent etiology (n = 19 patients). RESULTS: Untreated patients and patients undergoing pre-KTx plasma exchange prophylaxis had a relapse rate of 0.81 (CI 0.30-1.76) and 3.1 (CI 0.64-9.16) events per 10 years cumulative observation, respectively, as opposed to 0 events among patients receiving Eculizumab prophylaxis. The time between Eculizumab doses was tailored based on classic complement pathway activity (target to < 30%). Using this strategy, 12 patients are currently receiving  Eculizumab every 28 days, 5 every 24-25 days, and 3 every 21 days. CONCLUSION: Our experience supports the prophylactic use of Eculizumab in patients with a previous history of aHUS undergoing KTx, especially when complement dysregulation is well documented by molecular biology.

Haploidentical Hematopoietic Stem Cell Transplant Complicated by Atypical Hemolytic Uremic Syndrome and Kidney Transplant From the Same Donor With No Immunosuppression but C5 Inhibition.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is life-threatening condition particularly when complicating allograft hematopoietic stem cell transplant (HSCT). In the past, the outcome was very poor with the majority of patients reaching end-stage renal disease or dying with little or no chances of kidney transplant (KTx) due to the high risk of relapse. The availability of C5 inhibition has opened up significant therapeutic opportunities and has improved the outcome particularly if complement dysregulation (CD) is the underlying pathogenetic mechanism. METHODS: We describe a peculiar case of a girl with aHUS complicating HSCT and her subsequent successful KTx received from the same donor thus performed without immunosuppression but anti-C5 inhibition. RESULTS: Soon after HSCT performed for acute lymphoblastic leukemia, the patient developed a TMA due to CD and reached end-stage renal disease. After 2 years on dialysis, the patient received a KTx from her father who was already the HSCT donor. Given the full chimerism, no immunosuppressive agent was prescribed except a short (2 days) course of steroids and eculizumab to prevent aHUS relapse. Nine months after the KTx, the patient is well with normal renal function, no immunosuppression and continues eculizumab prevention of aHUS (1 infusion every 21 days). CONCLUSIONS: All patients with transplant-associated thrombotic microangiopathy should be screened for the causes of CD. C5 inhibition with eculizumab is an important therapeutic resource to manage this complication. When KTx is necessary, immunosuppression can be safely withhold in case of same donor for both grafts and documented full chimerism.

Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome: an update.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ damage. Eculizumab (ECU), a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule is not yet clear. METHODS: Here, we report our experience with ECU maintenance treatment and the interval between subsequent doses being extended based on global classical complement pathway (CCP) activity aimed at <30% for maintaining aHUS into remission. RESULTS: We report on 38 patients with aHUS, 13 children, 21 female, with a median age of 25.0 years (range 0.5-60) at disease onset treated with ECU standard schedule for a median of 2.6 months (range 0.4-24.6). Once stable TMA remission was obtained, the interval between ECU doses was extended based on complement function, with a target CCP activity of <30%. With this approach, 22 patients regularly receive ECU infusion every 28 days and 16 every 21. During a median observation period on ECU, an extended interval of 26.9 months (range 0.8-80.9), with a cumulative observation period of 1,208 months, none of the patients relapsed. CONCLUSION: Monitoring complement activity allows a safe reduction in the frequency of ECU administration in aHUS while keeping the disease in remission.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Posterior reversible encephalopathy syndrome after kidney transplantation in pediatric recipients: Two cases.

PRES is a neuro-clinical and radiological syndrome that can result as a consequence of several different conditions including hypertension, fluid overload, and immunosuppressive treatment. Herein, we report two children who received kidney and combined liver-kidney transplantation as treatment for renal hypodysplasia associated with bilateral vesico-ureteral reflux and methylmalonic acidemia, respectively. Early after surgery (seven and 10 days), both patients presented with hypertension and seizures. The patients' immunosuppressive regimen included steroid and calcineurin inhibitors (tacrolimus and cyclosporine, respectively) and basiliximab and one with anti-IL2 receptor. In both cases, the imaging strongly supported the diagnosis of PRES. In details, the CT scan showed hypodensities in the posterior areas of the brain, and brain MRI demonstrated parieto-occipital alterations indicative of vasogenic edema. Treatment with calcineurin inhibitors was temporally discontinued and restarted at lower dosage; arterial hypertension was treated with Ca-channel blockers. Both children fully recovered without any neurological sequels. In conclusion, in children undergoing solid organ transplantation, who develop neurological symptoms PRES, should be carefully considered in the differential diagnosis and once the diagnosis is ruled in, we recommend strict arterial blood pressure control and adjustment or withholding of calcineurin inhibitor therapy should be considered based upon blood levels.

What has changed in more than 40 years of activity and 3000 kidney transplants at Policlinico University Hospital, Milan.

The activity of kidney transplantation at Policlinico University Hospital, now the Ca' Granda Foundation, was established by Professor Edmondo Malan, who performed the first deceased donor transplantation in Milan, Italy, in 1969. Since then, 2989 kidney transplant procedures (2760 first, 219 second, 10 third transplants) have been performed through the end of November 2011, 2617 of them coming from deceased donors and 372 from living donors. Patient and graft survival have increased since the introduction of cyclosporine and tacrolimus in the last 28 years: 323 living donor-recipients under calcineurin inhibitors (CNI) show patient survival of 95.4% at five years and 88% at 10 years, not significantly different when compared with those of 1968 deceased donor-recipients (93.5% and 86.2%, respectively, at the same time points). Crude graft survival for living donor-recipients under CNI is 84.2% at 5 years and 70.2% at 10 years, not significantly different from those of deceased donor-recipients (80.3% and 64.3% for at the same time points). Actuarial graft survival censored by death is 87.2% at 5 years and 76.5% at 10 years for living donor-recipients vs. 84.4% and 72.2% for deceased donor-recipients, respectively. Previously unacceptable living or deceased kidneys are now successfully transplanted after being repaired with microsurgical techniques at bench. The rate of donors over 60 years of age has increased from 3.8% in the period of 1983-1995 to 20.8% in the last 15 years. It is interesting to note that 306 older kidneys (living donor, deceased donor, first, second, third transplants, with mean donor age of 64.6 +/- 4.0 yrs. and range 60-77 yrs.), always transplanted singularly, have similar behavior if compared with organs coming from donors aging 11-49 years. Survival rates are 93.1%, 90.1%, 88.4%, and 73.2% at 1, 3, 5, and 10 years post-transplant for the older donor grafts vs. 91.2%, 88.1%, 85.4%, and 74.4% for the younger donor grafts at the same time points. Perhaps the practice of dual transplant should be revisited and reserved to very old and ECD-donors. An open subcostal mini-incision (MINI) has been utilized in 177 living donors since 1996. This technique offers the same advantages of hand assisted videolaparoscopic technique, no disadvantages, and no major complications. Although more older and unrelated living donors are included in the MINI-group, very good results are obtained in these recipients, with graft survival censored by death of 97.2%, 95.3%, 93.8%, and 86.3% at 1, 3, 5, and 10 years post-transplant.