Mehmet Sukru Sever

International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology

Executive summary Acute kidney injury (AKI) is a major contributor to poor patient outcomes. AKI occurs in about 13·3 million people per year, 85% of whom live in the developing world, and, although no direct link between AKI and death has yet been shown, AKI is thought to contribute to about 1·7 million deaths every year. The course of AKI varies with the setting in which it occurs, and the severity and duration of AKI aff ects outcomes such as dialysis requirement, renal functional recovery, and survival. Recognition is increasing for the eff ect of AKI on patients, and the resulting societal burden from its longterm eff ects, including development of chronic kidney disease and end-stage renal disease needing dialysis or trans plantation. Few systematic eff orts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease. Several factors have contributed to the paucity of information. Most importantly, there have been few population-level epidemiological studies in several regions of the world. Diffi culties in defi nition of the incidence of AKI are especially evident in searches for data from low-income and middle-income countries, where more than 85% of the world’s population resides. No nationwide data collection systems are available, and data are usually from isolated centres and probably largely underestimate the true extent of AKI because they mostly do not include patients with AKI who were not able to reach a hospital for treatment. A recent metaanalysis that included 312 cohort studies and more than 49 million patients shows a scarcity of data from Africa and large parts of southeast Asia. We did an updated meta-analysis that used the most recent KDIGO (Kidney Disease: Improving Global Outcomes) defi nitions, which confi rms the high incidence and resulting outcomes of AKI, particularly in Africa, Asia, and Latin America, for which data were previously absent. The strong relation between the severity of AKI and consequent mortality is reiterated by our fi ndings and is evident across heterogeneous populations and specifi c disease cohorts. However, large gaps remain in knowledge about the factors that aff ect the geographical variation of AKI and poor outcomes. Many diff erences exist in the aetiology, pathophysiology, and management of AKI across the world. In high-income countries, AKI develops mainly in patients in hospitals. In low-income and middle-income countries, AKI occurs mainly in the community setting in acute illness, usually in association with diarrhoeal states and dehydration, infections such as malaria, and toxins (venoms and poisons). Public health issues (eg, contaminated water, poor sanitation, endemic infections such as malaria and dengue fever, venomous snakes, and toxic traditional medicines) and socioeconomic factors (eg, availability of health-care facilities) aff ect the epidemiology of AKI. Additionally availability of trained personnel and access to diagnostic tests and dialysis aff ect practice patterns and impose barriers to care. The extent to which these factors contribute to mortality and non-recovery of renal function has not been quantifi ed. AKI is potentially preventable and treatable with timely intervention, but there continues to be a high human burden. Which specifi c factors account for the poor outcomes and to what extent variations in care delivery contribute are unclear. The ability to provide lifesaving treatments for AKI provides a compelling argument to consider therapy for AKI as much of a basic right as it is to give antiretroviral drugs to treat HIV in low-resource regions, especially because care needs only be given for a Published Online March 13, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60126-X

Early and Vigorous Fluid Resuscitation Prevents Acute Renal Failure in the Crush Victims of Catastrophic Earthquakes

This study analyzes the effects of fluid resuscitation in the crush victims of the Bingol earthquake, which occurred in May 2003 in southeastern Turkey. Questionnaires asking about demographic, clinical, laboratory, and therapeutic features of 16 crush victims were filled in retrospectively. Mean duration under the rubble was 10.3 +/- 7 h, and all patients had severe rhabdomyolysis. Fourteen patients were receiving isotonic saline at admission, which was followed by mannitol-alkaline fluid resuscitation. All but two patients were polyuric. Admission serum creatinine level was lower than and higher than 1.5 mg/dl in 11 and 5 patients, respectively. Marked elevations were noted in muscle enzymes in all patients. During the clinical course, hypokalemia was observed in nine patients, all of whom needed energetic potassium chloride replacement. Four (25%) of 16 victims required hemodialysis. Duration between rescue and initiation of fluids was significantly longer in the dialyzed victims as compared with nondialyzed ones (9.3 +/- 1.7 versus 3.7 +/- 3.3 h, P < 0.03). Sixteen fasciotomies were performed in 11 patients (68%), nine of which were complicated by wound infections. All patients survived and were discharged from the hospital with good renal function. Early and vigorous fluid resuscitation followed by mannitol-alkaline diuresis prevents acute renal failure in crush victims, resulting in a more favorable outcome.

Endogenous Testosterone and Mortality in Male Hemodialysis Patients: Is It the Result of Aging?

BACKGROUND AND OBJECTIVES Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile. RESULTS Mean testosterone level was 8.69 ± 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P = 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P = 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses. CONCLUSIONS Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

The effect of calcineurin inhibitors on endothelial function in renal transplant recipients.

Abstract:  Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end‐stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty‐four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium‐dependent and ‐independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium‐dependent vasodilation was 12.1 ± 5.1% in group I and it was 6.5 ± 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 ± 6.3 and 12.7 ± 5.6% in groups I and II, respectively. This indicates that the endothelium‐dependent and ‐independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 ± 39.4 and 43.9 ± 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post‐transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.

Features of Chronic Hemodialysis Practice after the Marmara Earthquake

After disasters, treatment of chronic hemodialysis (HD) patients is problematic because of logistic and medical reasons. This study analyzes features of HD practice in the regions affected by the Marmara earthquake that struck northwestern Turkey in August 1999. Questionnaires asking about HD infrastructure, medical/social problems of chronic dialysis patients, and the fate of dialysis personnel after the disaster were sent to dialysis units located in the affected region. Data gathered from eight HD centers that responded to questionnaires were then analyzed. The number of HD centers and machines were 12 and 124, respectively, before the earthquake. The number of weekly HD sessions in the analyzed eight centers declined from 1093 before the disaster to 520, 616, and 729 1 wk, 1 mo, and 3 mo after the earthquake, respectively. In the effective seven centers, the number of HD personnel was 112 before the earthquake, which dropped to 86 and 94 1 and 3 mo after the disaster, respectively. Overall, there were 439 patients in the analyzed eight centers before the disaster, whereas data were provided on 356 (212 were male; mean age, 47.6 +/- 15.1 yr) dialysis patients. Six patients died, and seven were seriously and 28 mildly injured by the direct effects of trauma. The percentage of patients who received once-weekly dialysis increased from 2.3 to 7.2% within the first week, with a return to lower figures (4.1 and 2.8%) 1 and 3 mo afterward. Despite a decrease in the number of HD sessions, interdialytic weight gain decreased 1 wk after the disaster and BP measurements did not change significantly before and after the earthquake. A total of 301 and 31 patients left their dialysis centers, temporarily and permanently. After catastrophic earthquakes, despite a decrease in the number of HD sessions, patients comply with disaster conditions, likely by strictly following dietary and fluid restrictions.

Treatment Modalities and Outcome of the Renal Victims of the Marmara Earthquake

Background/Aims: Treatment of renal problems during natural catastrophes is highly complicated both for medical and logistic reasons. The therapeutic interventions applied to and the outcome of 639 victims with acute renal problems during the catastrophic Marmara earthquake have been the subject of this study. Methods: Questionnaires regarding information about 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information considering therapeutic interventions and outcome obtained through these questionnaires was submitted to analysis. Results: At least one form of renal replacement therapy was administered to 477 (74.6%) of the 639 victims. Of these, 437, 11, and 4 were treated solely by intermittent hemodialysis, continuous renal replacement therapy, and peritoneal dialysis, respectively; 25 victims needed more than one dialysis modality. In total, 5,137 hemodialysis sessions were performed. Also, 2,981, 2,837 and 2,594 units of blood, fresh frozen plasma, and human albumin were administered, respectively. Transfusion of these products was usually associated with higher rates of dialysis needs and mortality. Ninety-seven patients (15.2%) died. The mortality rate of dialyzed victims was higher as compared to nondialyzed ones (17.2 vs. 9.3%, p = 0.015). Conclusions: Massive amounts of dialysis treatment as well as blood and blood product transfusions can be necessary in the treatment of catastrophic earthquake victims with nephrological problems. Despite the potential risk of a high mortality, in the case of appropriate and energetic medical interventions, reasonable final outcomes can be achieved.

When the earth trembles in the Americas: the experience of Haiti and Chile 2010.

The response of the nephrological community to the Haiti and Chile earthquakes which occurred in the first months of 2010 is described. In Haiti, renal support was organized by the Renal Disaster Relief Task Force (RDRTF) of the International Society of Nephrology (ISN) in close collaboration with Médecins Sans Frontières (MSF), and covered both patients with acute kidney injury (AKI) and patients with chronic kidney disease (CKD). The majority of AKI patients (19/27) suffered from crush syndrome and recovered their kidney function. The remaining 8 patients with AKI showed acute-to-chronic renal failure with very low recovery rates. The intervention of the RDRTF-ISN involved 25 volunteers of 9 nationalities, lasted exactly 2 months, and was characterized by major organizational difficulties and problems to create awareness among other rescue teams regarding the availability of dialysis possibilities. Part of the Haitian patients with AKI reached the Dominican Republic (DR) and received their therapy there. The nephrological community in the DR was able to cope with this extra patient load. In both Haiti and the DR, dialysis treatment was able to be prevented in at least 40 patients by screening and adequate fluid administration. Since laboratory facilities were destroyed in Port-au-Prince and were thus lacking during the first weeks of the intervention, the use from the very beginning on of a point-of-care device (i-STAT®) was very efficient for the detection of aberrant kidney function and electrolyte parameters. In Chile, nephrological problems were essentially related to difficulties delivering dialysis treatment to CKD patients, due to the damage to several units. This necessitated the reallocation of patients and the adaptation of their schedules. The problems could be handled by the local nephrologists. These observations illustrate that local and international preparedness might be life-saving if renal problems occur in earthquake circumstances.

Lessons learned from the catastrophic Marmara earthquake: factors influencing the final outcome of renal victims.

BACKGROUND During catastrophic earthquakes, crush syndrome is the second most frequent cause of death after the direct impact of trauma. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 639 crush syndrome victims with acute renal problems. The factors influencing their final outcome have been the subject of this study. PATIENTS/METHODS Within the first week of the disaster questionnaires asking about 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information obtained by means of these questionnaires, including the factors with a potential influence on outcome, was submitted to analysis. RESULTS Overall mortality rate was 15.2%. In univariate analysis, nonsurvivors were older (p = 0.048); the highest mortality rates were observed among the victims coming from the closest cities to the reference hospitals. Admission within the first 3 days of the disaster (p = 0.016), with oliguria (p = 0.042), lower figures for blood pressure (p < 0.001), platelets (p = 0.004) and serum albumin (p = 0.005) were associated with mortality. Also, higher body temperature (p = 0.013) and serum potassium (p < 0.001) as well as suffering from thoracic or abdominal traumas, extremity amputations and medical complications other than renal failure (for all 4: p < 0.0001) in addition to need of dialysis support (p = 0.015) and mechanical ventilation (p < 0.0001) indicated higher risk of death. In the multivariate analysis, age (p = 0.030, OR = 1.02), presence of disseminated intravascular coagulation (p = 0.001, OR = 4.49), abdominal trauma (p = 0.012, OR = 4.05) and amputations (p = 0.010, OR = 2.81) were predictors of mortality. Dialyzed patients were characterized by higher mortality rates than nondialyzed victims (17.2% versus 9.3%, p = 0.015). CONCLUSION Outcome of the renal victims of catastrophic earthquakes is influenced by the type of trauma, comorbid events and complications observed during the clinical course as well as epidemiological features such as age, distance to reference hospitals and time lapse between disaster and admission to reference hospitals.

Infectious complications after mass disasters: the Marmara earthquake experience.

The Marmara earthquake occurred on 17 August 1999. There were 639 renal victims, of whom 477 needed some form of renal replacement therapy. Although several medical complications have been reported in the literature, there has been no detailed description of infectious complications in patients with crush syndrome after earthquakes. Data from 35 hospitals considering clinical and laboratory findings, as well as infectious complications and the results of microbiological examinations, were analysed. 223 out of 639 (34.9%) patients had infectious complications, which comprised the most frequent medical problem in the renal victims. The patients who suffered from infections had a higher mortality rate than those who did not (p=0.03). Sepsis and wound infection were the main presentation of the infectious complications. 121 (18.9%) patients suffered from sepsis; the mortality rate was higher in these patients (27.3%) than in victims who did not suffer from sepsis (12.4%, p<0.0001). In a multivariate model, sepsis was associated with increased mortality (p=0.0002, odds ratio 2.45, 95% confidence interval 1.52–3.96). 53 (8.2%) and 41 (6.4%) patients had wound and pulmonary infections, respectively. Most of the infections were nosocomial in origin and caused by Gram-negative aerobic bacteria and Staphylococcus spp. Infectious complications are common in renal victims of catastrophic earthquakes and are associated with increased mortality when complicated by sepsis.

Helicobacter pylori antibodies in hemodialysis patients and renal transplant recipients

In this cross‐sectional, controlled study, Helicobacter pylori (H. pylori) infection, a probable factor in the development of gastrointestinal problems, was investigated in dialysis patients and renal transplant recipients. Forty‐seven dialysis patients (22 male, 25 female, mean age of 36.6±15 yr (range 18–83 yr)), 57 renal transplant recipients (39 male, 18 female, mean age of 36.8±10 yr (range 19–60 yr)) and 55 healthy individuals (34 male, 21 female, mean age of 33.4±9.6 yr (range 21–58 yr)) were included and no significant difference was found in the study groups. The mean time spent on dialysis in the hemodialysis group was 32.5±27.7 months (range 1–100 months). H. pylori antibodies were detected in 22 of 57 (38.6%) patients in the transplantation group, 31 of 47 (65.9%) patients in the dialysis group and 39 of 55 (72.5%) in the control group. No correlation was found between H. pylori infection and age, sex, primary disease, frequency of dialysis, duration and type of transplantation and the immunosuppressive therapy. However, patients with H. pylori antibodies spent a shorter time on dialysis compared to patients without the antibodies (26.6±23.5 vs 44.1±32.1 months, p=0.038). The frequency of H. pylori infection in the transplantation group was significantly lower than the control and dialysis groups (p<0.01). This finding may be explained on the basis of decreased humoral antibody response to H. pylori infection, secondary to immunosuppressive therapy rather than decreased incidence of infection in the transplantation group. Finally, we concluded that the value of the serological test for diagnosis of H. pylori infection should be interpreted cautiously in these patient groups.