Joerg Latus

Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis–experience of a referral centre in Germany

BACKGROUND Chronic peritoneal dialysis (PD) can be complicated by encapsulating peritoneal sclerosis (EPS), the most severe complication associated with long-term PD. METHODS In this study, we retrospectively analysed 49 EPS patients regarding clinical presentation, histopathological findings, treatment and long-term clinical outcome at our referral centre. Patients were divided into two clinical categories: severe and mild/moderate. RESULTS All patients in the severe group and most patients in the mild/moderate group had symptoms consistent with EPS. The most common computed tomographic findings were peritoneal thickening in both groups. Small bowel dilatation was frequently present in the severe group. The time of onset of symptoms consistent with EPS to the surgical procedure was median 5 months with an inter-quartile range of 2-12 months in the severe group. To date, 25 of 31 patients in the severe group (follow-up 45.6 ± 39.0 months after surgery) are alive. In the mild/moderate group, 8 of 11 patients are alive (follow-up 41.6 ± 21.6 months). The histological features were consistent with EPS in all biopsies. CONCLUSIONS The outcome of patients even with severe EPS is not worse. It is a precondition that these patients are treated in specialized referral centres. The time of first clinical symptoms consistent with EPS to requirement of surgery is very short. Earlier diagnosis of the disease is mandatory, even in asymptomatic patients.

Acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica

BACKGROUND Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patients.

Efficacy and morbidity of surgical therapy in late-stage encapsulating peritoneal sclerosis

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis composed of chronic abdominal pain, chronic ileus, and severe malnutrition. Operative therapy for EPS is a complex procedure, including perionectomy and enterolysis (PEEL). In contrast to simple adhesiolysis, PEEL comprises a restitution of intestinal passage and prevention of recurrent disease by decapsulation and partial deserosation. METHODS We reviewed the treatment of patients with EPS at our referral center regarding perioperative morbidity, mortality, and long-term outcome. Only patients who underwent PEEL were included. Preoperative general status was ascertained by APACHE-II score and body mass index. Postoperative morbidity was stratified into minor and major complications. RESULTS Between the years 2003 and 2010, 26 of 45 patients with late-stage EPS underwent PEEL. Median age was 54 years, APACHE-II score was 15, and body mass index was 21 kg/m². To achieve intestinal function, 9 bowel resections with immediate anastomoses were necessary. Eleven patients (37%) received a complete parietal peritonectomy. Overall morbidity was 44%, with minor complications in 2 patients (7%) and major complications in 11 patients (31%). Three patients (10%) died within the first year after operative treatment. CONCLUSION PEEL is a treatment option that can be performed with low mortality and acceptable morbidity. It is a precondition that these patients are treated in specialized referral centers.

Incidence of and risk factors for hungry bone syndrome in 84 patients with secondary hyperparathyroidism

Introduction Secondary hyperparathyroidism develops in nearly all patients with end-stage renal disease. Parathyroidectomy is often performed when medical therapy fails. The most common postoperative complication, hungry bone syndrome (HBS), requires early recognition and treatment. Materials and methods A total of 84 patients who underwent parathyroidectomy because of secondary hyperparathyroidism were investigated. Detailed analysis of laboratory parameters (calcium, phosphate, parathyroid hormone, hemoglobin, and urea levels) and baseline characteristics (age at time of surgery, duration of renal replacement therapy, and medication) was performed to detect preoperative predictors for the development of HBS. Results Average overall follow-up of the cohort was 4.7 years. Within this time frame, 13 of 84 patients had to undergo a second surgery because of recurrent disease, and HBS occurred in 51.2%. Only decreased preoperative calcium levels and younger age at time of surgery were significant predictors of HBS. Minimal levels of calcium were detected 3 weeks after surgery. Preoperative vitamin D therapy could not prevent HBS and could not shorten the duration of intravenous calcium supplementation. Conclusion HBS is a very common complication after parathyroidectomy. Younger patients and patients with low preoperative calcium levels were at higher risk for the development of HBS. Remarkably, preoperative vitamin D therapy could not prevent HBS and had no impact on the length of intravenous calcium supplementation. Intensive monitoring of calcium levels must be performed for at least 3 weeks after surgery.

Histological criteria for encapsulating peritoneal sclerosis - a standardized approach.

Background The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS Methods We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients. Results The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%. Conclusion The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.

Drug-induced acid-base disorders

The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk–alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine).

Early stages of calciphylaxis: are skin biopsies the answer?

Calciphylaxis, nowadays called calcific uremic arteriolopathy (CUA), is a rare but life-threatening syndrome characterized by systemic medial calcification and arterial occlusion of the arterioles, leading to skin necrosis. Actually, the pathogenesis of CUA is complex and poorly understood. The vast majority of published cases presented with ulcers. We present a 71-year-old male who was referred to the Nephrology Department for evaluation and therapy for refractory edema of both legs. There were no subcutaneous plaques, ulcers or other focal lesions. We performed a deep skin biopsy of the thigh. After the biopsy, the patient developed necrosis around the sampling location. Diagnosing CUA in the early stages of the disease, however, is challenging. Should a skin biopsy be performed in the early stages of CUA in patients without ulcerations, knowing the risk of inducing ulcerations, or should an intensive treatment – after considering clinical manifestations, other noninvasive diagnostic tools (bone scan, X-ray mammography technique) and laboratory tests – be started? Although there are no specific diagnostic laboratory tests for CUA and the clinical manifestations of CUA are similar to those of other disorders, a skin biopsy is not routinely recommended to confirm the diagnosis of early-stage calciphylaxis.

Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department

BACKGROUND AND OBJECTIVES Emergency departments (EDs) have a growing role in hospital admissions, but few studies address AKI biomarkers in the ED. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients admitted to the internal medicine service were enrolled during initial workup in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) and urine output (UO) were recorded for AKI classification by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cystatin C, kidney injury molecule-1, liver-type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were measured in blood and urine, and IL-18, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and [TIMP-2]⋅[IGFBP7] were measured in urine collected at enrollment, after 6 hours, and the following morning. Association between these biomarkers and the end point of moderate-severe AKI (KDIGO stage 2-3) occurring within 12 hours of each sample collection was examined using generalized estimating equation logistic regression. Performance for prediction of the AKI end point using two previously validated [TIMP-2]-[IGFBP7] cutoffs was also tested. RESULTS Of 400 enrolled patients, 298 had sufficient sCr and UO data for classification by KDIGO AKI criteria: AKI stage 2 developed in 37 patients and AKI stage 3 in nine patients. All urinary biomarkers, sCr, and plasma cystatin C had statistically significant (P<0.05) odds ratios (ORs) for the AKI end point. In a multivariable model of the urine biomarkers and sCr, only [TIMP-2]⋅[IGFBP7] and sCr had statistically significant ORs. Compared with [TIMP-2]⋅[IGFBP7]<0.3 (ng/ml)(2)/1000, values between 0.3 and 2.0 (ng/ml)(2)/1000 indicated 2.5 (95% confidence interval [95% CI], 1.1 to 5.2) times the odds for the AKI end point and values >2.0 (ng/ml)(2)/1000 indicated 11.0 (95% CI, 4.4 to 26.9) times the odds. Addition of [TIMP-2]⋅[IGFBP7] to a clinical model significantly improved area under the receiver-operating characteristic curve from 0.67 (95% CI, 0.61 to 0.78) to 0.77 (95% CI, 0.72 to 0.86) (P<0.001); however, including both markers in the model was not significantly different from including either marker alone. CONCLUSIONS Urinary [TIMP-2]⋅[IGFBP7] with pre-established cutoffs provides valuable information about risk for imminent AKI in the ED that is complementary to sCr and clinical risk factors.

Severe thrombocytopenia in hantavirus-induced nephropathia epidemica

Nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome, caused by Puumala virus. The clinical picture is characterized by a rapid loss of renal function (acute kidney injury) and thrombocytopenia. The purpose of the current analysis was to compare the clinical course of patients presenting with or without severe thrombocytopenia. In 47 out of 456 patients with acute nephropathia epidemica, the nadir count of thrombocytes was available for the acute course of the disease. The clinical course of these patients was further analyzed. No major bleeding (e.g., intracranial bleeding or gastrointestinal bleeding) occurred in either group. Creatinine peak levels were higher and proteinuria was more frequently present in the severely thrombocytopenic group. In conclusion, severe thrombocytopenia is common in nephropathia epidemica and is associated with a more severe course of the disease; however, bleeding complications are rare.

Clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, Germany.

The consequences of associated hematuria may be long-lasting, and hantavirus IgG is detectable years after acute infection.