H Haller

Publications (218)1032.96 Total impact

• Article: [Acute tubulointerstitial nephritis as hyperergic reaction of the kidneys].

  A Schwarz, J U Becker, H Haller
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  ABSTRACT: Acute tubulointerstitial nephritis was formerly only observed during the early phase of infections. With the emergence of antibiotics this disease became a rarity. In contrast the importance of drug-associated acute tubulointerstitial nephritis grew in importance and is now the most common form and expression of a hyperergic reaction of the kidneys. Acute tubulointerstitial nephritis occurs as a third form in cases of systemic autoimmune diseases, e.g., in idiopathic tubulointerstitial nephritis or within the scope of Sjögrens syndrome with distal tubular acidosis. The common symptoms of the drug-induced form are fever, side pain, microhematuria or macrohematuria and a mostly sharp increase in creatinine levels but to a greatly differing extent. Histologically, there is interstitial edema and interstitial lymphocyte-rich infiltration with tubulitis. The symptoms can be subclinical or even non-existent. In most case remission occurs, sometimes only partial remission or transformation to chronic interstitial nephritis. Risk factors are for example delayed diagnosis, recurrent episodes and the accompanying use of analgesics. The more acute and intense the clinical symptoms are, the earlier the diagnosis and therefore the better the prognosis. A temporary steroid treatment can promote regression.
  Der Internist 07/2012; 53(8):934, 936-7, 939-41. · 0.30 Impact Factor
• Article: Tubulointerstitielle Fibrose

  V. Bröcker, H. Kreipe, H. Haller
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  ABSTRACT: Der Begriff interstitielle Fibrose und Tubulusatrophie (IFTA) beschreibt die uniforme Vernarbung des Interstitiums der Niere, die für sich genommen nicht spezifisch für eine zugrunde liegende Erkrankung ist. Sowohl primär glomeruläre als auch primär interstitielle Erkrankungen der Niere (letztere sind deutlich seltener) führen bei chronischem Verlauf gleichermaßen zu IFTA. Dabei bestimmt das Ausmaß der Fibrose wesentlich die Prognose der Erkrankung. Verschiedene Mechanismen für die Entstehung von IFTA, ausgehend von glomerulären Schäden, welche die Bowman-Kapsel einbeziehen, Hypoxie, epithelial-mesenchymale/endothelial-mesenchymale/perizytär-mesenchymale Transdifferenzierung werden diskutiert. IFTA stellt keine Diagnose dar, sondern beschreibt eine vermutlich irreversible Reaktion der Niere auf verschiedene Schädigungen. Interstitial fibrosis and tubular atrophy (IFTA) represent uniform scarring of the interstitial zone of the kidney that is not restricted to a specific disorder. Glomerular as well as primary interstitial disorders lead to IFTA, as they progress to pursue a chronic course. Primary interstitial diseases are much rarer compared to glomerular diseases. The extent of fibrosis mainly determines the prognosis and outcome of renal diseases in general. Different mechanisms have been proposed to explain the development of IFTA: evolvement from glomerular damage that involves Bowman’s capsule, hypoxia, epithelial-mesenchymal, endothelial-mesenchymal and pericytic-mesenchymal transition. IFTA is not a specific diagnosis but forms a final common track of different modalities of damage, which is most likely irreversible. SchlüsselwörterInterstitielle Fibrose und Tubulusatrophie-IFTA-Interstitielle Nephritis-Glomerulonephritis-Epithelial-mesenchymale Transdifferenzierung-Endothelial-mesenchymale Transdifferenzierung-Perizytär-mesenchymale Transdifferenzierung KeywordsInterstitial fibrosis and tubular atrophy-IFTA-Interstitial nephritis-Glomerulonephritis-Epithelial-mesenchymal transition-Endothelial-mesenchymal transition-Pericytic-mesenchymal transition
  Der Nephrologe 05/2012; 5(4):284-292.
• Article: Erworbene zystische Nierenerkrankung

  A. Schwarz, M. Hiss, J.U. Becker, H. Haller
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  ABSTRACT: Die erworbene zystische Nierenveränderung kann als Versuch einer kompensatorischen Regeneration des Tubulusepithels bei Niereninsuffizienz verstanden werden und führt zur zystischen Umwandlung der versagenden Niere bei 30 bis 90% von Patienten mit terminaler Niereninsuffizienz in Abhängigkeit von der Länge der Dialysedauer, unabhängig von der Art der Nierenerkrankung. Zysteneinblutungen, Zystenrupturen oder Infektionen sind eher selten. Das eigentliche Problem dieser zystischen Veränderung ist ihr Übergang in eine sogenannte komplizierte Zyste und dann in ein Karzinom. Patienten mit zystischer Nierenveränderung nach Nierentransplantation entwickeln eigener Erfahrungen zufolge in 20% der Fälle ein Nierenzellkarzinom. Dieses ist in der Regel eher ein papilläres als ein hellzelliges Karzinom, ist vom Verlauf her deutlich gutartiger als das sporadische Karzinom und hat einen anderen genetischen Hintergrund. Die Nieren von Patienten mit terminaler Niereninsuffizienz sollten jährlich, bei Vorhandensein von Zysten halbjährlich sonographisch kontrolliert werden im Hinblick auf die Entstehung eines Karzinoms. Acquired cystic kidney disease (ACKD) develops from regenerating dilated tubular epithelium in patients with renal insufficiency and ends up in the cystic degeneration of the kidney in 30%–90% of patients with end-stage renal disease, depending on the length of time on dialysis, but regardless of type of renal disease. Bleeding, rupture or infection of the cysts are rare. The real problem posed by this cystic degeneration is the transition to complicated cysts and then to renal cell carcinoma. Patients with ACKD after renal transplantation developed renal cell carcinoma in 20% of cases (own experience). The tumour is more often a papillary than a clear cell carcinoma and, in contrast to sporadic renal cell carcinoma, usually has a more benign course; its genetic background is also different. Patients with end-stage renal disease should be checked by ultrasound of the kidneys annually and, if cysts are present, every six months to exclude renal cell carcinoma. SchlüsselwörterErworbene zystische Nierenerkrankung-Komplizierte Nierenzyste-Nierenzellkarzinom KeywordsAcquired cystic kidney disease-Renal cell carcinoma-Complicated renal cyst
  Der Nephrologe 05/2012; 5(5):396-403.
• Article: Amyloidosen in der Nephrologie – vielfältige Ablagerungen und bunte klinische Bilder

  V. Bröcker, H. Haller
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  ABSTRACT: Die Amyloidosen sind eine heterogene Gruppe von Erkrankungen, die sich in der Niere mit typischen Ablagerungen in Form von ultrastrukturellen Fibrillen darstellen. Die kongorot positiven Ablagerungen sind erstmals von Rudolf Virchow beschrieben worden und wurden damit definiert. Inzwischen hat sich gezeigt, dass diese Ablagerungen in ihrer Zusammensetzung unterschiedlich aufgebaut sind. Die Krankheiten zeichnen sich durch eine überschüssige Proteinproduktion verbunden mit einem Faltungsdefekt aus. Je nach Struktur des Ursprungmoleküls kann es 1.)zur typischen Faltblattstruktur mit Fibrillenbildung, 2.)zu atypischen Fibrillen oder 3.)zur ungeordneten Ablagerung der Ausgangsmoleküle kommen. Kompliziert wird die Erscheinungsform der Amyloiderkrankungen, weil bei gleichem Ausgangsmolekül (z.B. Immunglobulin-Leichtketten) unterschiedliche Aggregationszustände der Ablagerungen auftreten können, wie Immundeposits, Amyloid oder ausgefallene Proteine im Tubulus (Casts). In der Vergangenheit sind die Amyloidosen als typische passive Ablagerungserkrankungen betrachtet worden. Die Forschung der letzten Jahre zeigt, dass die frühen Proteinaggregate Zellen und Gewebe direkt schädigen können. Dies bedeutet, dass die Erkrankung der Nieren und anderer Organe bereits lange vor der Ablagerung auftritt und das Amyloid, das die Erkrankung ursprünglich definiert hat, eine späte Komplikation einer „Proteinfaltungserkrankung“ darstellt. Amyloidosis comprises a group of diseases characterized by the deposition of insoluble protein fibrils in various organs and tissues. These deposits were first described by Rudolf Virchow and have since been shown to take on various structures. The diseases are remarkable by an excess protein production in combination with defective folding. Depending on the structure of the origin molecule, the appearance may be of typical “cross beta sheet” fibril development, atypical fibrils, or assymmetrical deposits. The forms taken by the different amyloidoses are further complicated in that different deposit aggregations can appear from the same source molecule. Amyloidoses used to be seen as typical passive deposit disorders. In recent years however research has shown that the early protein aggregates can directly harm cells or tissure. That means that the disease in kidneys and other organs has begun long before the deposits are recognized, and that the amyloid giving the disease its name is in fact a late complication of a protein “folding” disorder.
  Der Nephrologe 05/2012; 3(4):268-274.
• Article: Fibrosierende Erkrankungen

  H. Haller, W.L. Gross
  Der Internist 05/2012; 51(1):5-5. · 0.30 Impact Factor
• Article: Fehldiagnosen in der Nephrologie

  A. Schwarz, H. Haller
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  ABSTRACT: Fehldiagnosen in der Nephrologie sind, wie in anderen Fächern der inneren Medizin, keine Seltenheit. Typische “nephrologische” Fehldiagnosen sind jedoch schwieriger zu definieren. Falsche Diagnosen bei untypischer Symptomatik, Unerfahrenheit des Arztes und unsystematischer Untersuchung sollen hier nicht besprochen werden. “Akutes Nierenversagen” durch übersehenen Harnstau bei Prostataadenom kann dafür ein Beispiel sein und stellt keine typische “nephrologische” Fehldiagnose dar. Zu den von uns gewählten Kriterien einer typischen Fehldiagnose zählt eine gewisse klassische Fehlinterpretation von Krankheitssymptomen und -verlauf. Solche Fehldiagnosensind auch erfahrenen Nephrologen schon begegnet und beinhalten retrospektiv eine Evidenz. Ein weiteres Kriterium der Fehldiagnose ist deren Bedeutung für den klinischen Verlauf. Wir haben im Folgenden solche Fälle gewählt, in denen die Fehldiagnose schwerwiegende, teilweise fatale Folgen für die Patienten hatte. Aus diesen Fehldiagnosen zu lernen ist nicht nur eine akademische Übung, sondern notwendige Ausbildung für den verantwortungsbewussten Arzt.
  Der Internist 04/2012; 43(5):595-606. · 0.30 Impact Factor
• Article: Aktuelle Probleme der Nierentransplantation

  H. Haller, N. Richter, V. Bröcker, W. Gwinner, F. Gueler, A. Schwarz
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  ABSTRACT: Die Langzeitprobleme nach Nierentransplantation haben sich in den letzten Jahren wesentlich geändert. Während früher v.a. die Immunsuppression und die Verhinderung der akuten Abstoßung im Vordergrund stand, sind es nun die chronischen Veränderungen im Transplantat und das Langzeitüberleben der Patienten. Die eigentliche Transplantation ist zu einem standardisierten Verfahren auf hohem chirurgischem Niveau geworden. Probleme der Organpräservation und des Ischämie/Reperfusionsschadens spielen ebenfalls v.a. unter chronischen Gesichtspunkten eine Rolle. Die Überwachung der Langzeitprobleme muss zum einen durch ein Programm für das transplantierte Organ und zum anderen durch ein Patientenprogramm erfolgen. Die Überwachung der Nierenfunktion sollte genauer als bisher das Organ erfassen. Serumkreatinin und Proteinurie sind allein zu wenig aussagefähig und verändern sich erst lange nach dem Beginn der zellulären Schädigung. Entsprechend sind dringend neue Untersuchungsmethoden zu entwickeln. Eine Möglichkeit eröffnen Protokollbiopsien, bei denen die Niere regelmäßig histologisch und molekular analysiert werden kann. In den Patientenprogrammen steht die Diagnostik und Therapie der kardiovaskulären Erkrankungen im Vordergrund. Daneben müssen die Patienten bezüglich des Auftretens von Neoplasien gescreent werden. Für alle kardiovaskulären Risikofaktoren nach Nierentransplantation fehlen prospektive Studien. Dies gilt insbesondere für den Bereich der Hypertonie. The long-term problems after kidney transplantation have changed considerably in recent years. While formerly immunosuppression and prevention of acute rejection were of prime concern, now attention focuses on chronic alterations of the transplanted organ and long-term survival of the patients. The transplantation procedure itself has evolved into a standardized technique with a high level of surgical quality. Problems involving organ preservation and ischemia/reperfusion damage also play a role, especially in view of chronic aspects. Monitoring of long-term complications should follow a program for the transplanted organ as well as a program for the patient. Monitoring kidney function should address the organ more precisely than has previously been the case. Serum creatinine level and proteinuria alone provide insufficient information and only change long after cellular deterioration has begun. Hence it is imperative that new testing methods be developed. One possibility is offered by protocol biopsies that allow histological and molecular analysis of the kidney at regular intervals. The patient programs concentrate on diagnostics and treatment of the cardiovascular diseases. Furthermore, the patients must be screened for occurrence of neoplasia. There are no prospective studies covering all cardiovascular risk factors after kidney transplantation. This pertains particularly to the subject of hypertension.
  Der Internist 04/2012; 50(5):523-535. · 0.30 Impact Factor
• Article: ANCA-assoziierte Vaskulitiden Neue Konzepte und Strategien in der Therapie

  K. de Groot, M. Haubitz, H. Haller
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  ABSTRACT: · die Wegenersche Granulomatose (WG), · die mikroskopische Polyangiitis (MPA) und · das Churg-Strauss-Syndrom (CSS). Dank verbesserter diagnostischer Maßnahmen (ANCA-Serologie, Immunhistochemie, bildgebende Diagnostik, z. B. CT und MRT) hat die Diagnosefrequenz der AAV innerhalb der letzten 20 Jahren sehr zugenommen [1]. Da die Erkrankung somit bereits vor Eintreten des Vollbildes einer rapid-progressiven Glomerulonephritis oder eines pulmorenalen Syndroms diagnostiziert werden kann, ist eine differenzierte, stadien- und aktivitätsadaptierte Therapie der AAV unbedingt erforderlich.
  Der Internist 04/2012; 41(10):1112-1119. · 0.30 Impact Factor
• Article: Renal comorbidity after solid organ and stem cell transplantation.

  C Clajus, N Hanke, J Gottlieb, M Stadler, T J Weismüller, C P Strassburg, V Bröcker, C Bara, F Lehner, J Drube, J T Kielstein, A Schwarz, F Gueler, H Haller, M Schiffer
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  ABSTRACT: After transplantation of solid organs or hematopoietic stem cells, a significant acute decrease in renal function occurs in the majority of patients. Depending on the degree of kidney injury, a large number of patients develop chronic kidney disease (CKD) and some develop end-stage renal disease requiring renal replacement therapy. The incidence varies depending on the transplanted organ, but important risk factors for the development of CKD are preexisting renal disease, hepatitis C, diabetes, hypertension, age, sex, posttransplant acute kidney injury and thrombotic microangiopathy. This review article focuses on the risk factors of posttransplant chronic kidney disease after organ transplantation, considering the current literature and integrates the incidence and the associated mortality rates of acute and chronic kidney disease. Furthermore, we introduce the RECAST (REnal Comorbidity After Solid organ and hematopoietic stem cell Transplantation) registry.
  American Journal of Transplantation 04/2012; 12(7):1691-9. · 6.39 Impact Factor
• Article: CXCL13 as a novel marker for diagnosis and disease monitoring in pediatric PTLD.

  L Schiffer, C Henke-Gendo, N Wilsdorf, K Hussein, L Pape, C Schmitt, H Haller, M Schiffer, C Klein, H Kreipe, B Maecker-Kolhoff
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  ABSTRACT: Posttransplant lymphoproliferative disease (PTLD) is a severe complication of immunosuppressive treatment in organ-grafted children. Early diagnosis of PTLD is hampered by both unspecific clinical symptoms and lack of easy accessible markers. The homeostatic chemokine CXCL13, which plays a crucial role in B-cell homing and lymphoid organ development, is expressed in some lymphomatous diseases. This study aims to investigate whether serum CXCL13 (sCXCL13) levels correlate with occurrence and regression of PTLD in pediatric solid-organ graft recipients. Serum samples from PTLD patients (n = 21), patients with Epstein-Barr virus (EBV) reactivation (n = 18), and healthy age-matched controls (n = 19) were tested for CXCL13 using a commercially available ELISA kit. sCXCL13 levels were significantly higher in PTLD patients than in healthy children. PTLD patients had also higher sCXCL13 values than pediatric solid-organ recipients with EBV reactivation. An increase in sCXCL13 levels was observed from EBV reactivation to PTLD diagnosis in most cases. Elevated sCXCL13 levels were detected up to 2 years prior to PTLD diagnosis and correlated well with response to cytoreductive treatment in individual patients. sCXCL13, thus, may be a readily available surrogate marker for the diagnosis of PTLD and for monitoring of response to treatment in patients with initially elevated sCXCL13 levels.
  American Journal of Transplantation 02/2012; 12(6):1610-7. · 6.39 Impact Factor
• Article: [Common infections in internal medicine].

  H Haller
  Der Internist 09/2011; 52(9):1025. · 0.30 Impact Factor
• Article: Urinary miR-210 as a mediator of acute T-cell mediated rejection in renal allograft recipients.

  J M Lorenzen, I Volkmann, J Fiedler, M Schmidt, I Scheffner, H Haller, W Gwinner, T Thum
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  ABSTRACT: MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. Circulating miRNAs are remarkably stable in the blood. We tested whether miRNAs are also detectable in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection. We profiled urinary miRNAs of stable transplant patients and transplant patients with acute rejection. The miR-10a, miR-10b and miR-210 were strongly deregulated in urine of the patients with acute rejection. We confirmed these data in urine of a validation cohort of 62 patients with acute rejection, 19 control transplant patients without rejection and 13 stable transplant patients with urinary tract infection by quantitative RT-PCR. The miR-10b and miR-210 were downregulated and miR-10a upregulated in patients with acute rejection compared to controls. Only miR-210 differed between patients with acute rejection when compared to stable transplant patients with urinary tract infection or transplant patients before/after rejection. Low miR-210 levels were associated with higher decline in GFR 1 year after transplantation. Selected miRNAs are strongly altered in urine of the patients with acute renal allograft rejection. The miR-210 levels identify patients with acute rejection and predict long-term kidney function. Urinary miR-210 may thus serve as a novel biomarker of acute kidney rejection.
  American Journal of Transplantation 08/2011; 11(10):2221-7. · 6.39 Impact Factor
• Article: [Diabetic nephropathy].

  J Menne, H Haller
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  ABSTRACT: Diabetic nephropathy is the most common cause of end-stage renal disease. Since the disease progresses very slowly and usually takes more than 20 years before terminal renal failure occurs, early intervention is of great importance in order to prevent this disabling complication. A good control of diabetes with HbA(1c) levels around 7% is desirable. At least as important is the treatment of elevated blood pressure values. The target value for patients with diabetes has been adjusted in the last year and is now 130-139/80-85 mmHg. Should (micro-)albuminuria or renal insufficiency be present the blood pressure target is <130/80 mmHg. For the control of hypertension the use of ACE inhibitors or angiotensin receptor blockers is recommended. In addition, the control of other risk factors and appropriate therapeutic intervention is required. A multifactorial intervention leads to the best results and can avoid the occurrence or progression of diabetic kidney disease and other micro- and/or macrovascular complications.
  Der Internist 05/2011; 52(5):495-504. · 0.30 Impact Factor
• Article: The molecular phenotype of 6-week protocol biopsies from human renal allografts: reflections of prior injury but not future course.

  M Mengel, J Chang, D Kayser, W Gwinner, A Schwarz, G Einecke, V Broecker, K Famulski, D G de Freitas, L Guembes-Hidalgo, B Sis, H Haller, P F Halloran
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  ABSTRACT: We assessed the molecular phenotype of 107 6-week protocol biopsies from human renal allografts, using Affymetrix microarrays. Transcript changes were summarized as nonoverlapping pathogenesis-based transcript sets (PBTs) reflecting inflammation (T cells, macrophages, IFNG effects) and the injury-repair response of the parenchyma, stroma and microcirculation-increased ('injury-up') and decreased ('injury-down') transcripts. The molecular changes were highly correlated with each other, even when all rejection and borderline cases were excluded. Inflammation and injury-down PBTs correlated with histologic inflammation and tubulitis, and the inflammation transcripts were greater in kidneys diagnosed as T cell-mediated or borderline rejection. Injury-up PBTs did not correlate with histopathology but did correlate with kidney function: thus functional disturbances are represented in transcript changes but not in histopathology. PBT changes correlated with prior delayed graft function. However, there was little difference between live donor kidneys and deceased donor kidneys that had not shown delayed graft function. Molecular changes did not predict future biopsies for clinical indications, rejection episodes, functional deterioration or allograft loss. Thus while detecting T cell-mediated inflammation, the molecular phenotype of early protocol biopsies mostly reflects the injury-repair response to implantation stresses, and has little relationship to future events and outcomes.
  American Journal of Transplantation 11/2010; 11(4):708-18. · 6.39 Impact Factor
• Article: Elevation of serum CXCL13 in SLE as well as in sepsis.

  L Schiffer, J T Kielstein, M Haubitz, H Lührs, T Witte, H Haller, P Kümpers, M Schiffer
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  ABSTRACT: Recent studies have demonstrated that CXCL13 serum levels correlate significantly with systemic lupus erythematosus (SLE) disease activity. However, experimental studies show that CXCL13 production can also be induced by bacterial exposure as well as in response to inflammatory cytokines. This report asks whether CXCL13 serum levels are elevated in patients with evidence of bacterial infections and whether there is a correlation with the C-reactive protein (CRP) levels or the severity of illness in critically ill patients. CXCL13 levels were compared in 39 patients with active SLE (without concomitant infection), 40 non-SLE patients with sepsis, and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA) methodology. We also tested storage conditions and freeze-thaw cycles for stability of CXCL13 in serum samples. Our studies demonstrated that the median CXCL13 serum levels were significantly elevated in patients with SLE [median 83 pg/ml (interquartile range 38-366)] or sepsis [359 pg/ml (151-459)] compared with healthy controls [32 pg/ml (27-41), p < 0.001]. The CXCL13 serum levels correlated with disease activity in SLE (CXCL13 vs. SLEDAI r = 0.65, p < 0.001), but were not associated with severity of illness score in critically ill patients (CXCL13 vs. SOFA r = -0.15, p = 0.35). However, CXCL13 serum levels were clearly associated with CRP levels in both sepsis (r = 0.45, p = 0.003) and SLE (r = 0.39, p = 0.02). In conclusion, CXCL13 is a stable serum marker for disease activity in SLE patients, but concomitant infections can also lead to increased CXCL13 levels.
  Lupus 11/2010; 20(5):507-11. · 2.34 Impact Factor
• Article: The angiopoietin/Tie-2 axis: a novel player in chronic kidney disease.

  S David, H Haller, P Kümpers
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  ABSTRACT: The development of atherosclerosis in patients with chronic kidney disease (CKD) is severely accelerated leading to life-threatening cardiovascular (CV) events and its pathogenesis is different from that in the general population. Mainly the so-called uremic toxins are thought to count responsible for this phenomenon. Recently, the angiopoietin/Tie2 system has been identified as a potential new player in the uremia-associated pathogenesis of atherosclerosis. This review provides an overview of molecular mechanisms of angiopoietin-1/-2 and Tie2 signaling in regard to the endothelial activation status in health and disease. The first part reviews the role of angiopoietins in experimental models of inflammation. Then, we summarize the most important clinical trials showing a severely altered angiopoietin balance in favor of Ang-2. Those trials contain data on patients with CKD stage 1-4, on dialysis (CKD stage 5), arterial hypertension, and diabetes mellitus. Future experiments to prove a direct mechanism by which angiopoietins accelerate and/or aggravate atherosclerotic burden in CKD patients are highly desirable. Very recently, a clinical trial (in oncology) proved safety of a selective angiopoietin inhibitor. Those latest drugs might represent a future treatment option against CKD-associated micro-inflammation.
  Minerva urologica e nefrologica = The Italian journal of urology and nephrology 09/2010; 62(3):319-26.
• Article: Biopsy-diagnosed renal disease in patients after transplantation of other organs and tissues

  A. Schwarz, H. Haller, R. Schmitt, M. Schiffer, C. Koenecke, C. Strassburg, F. Lehner, J. Gottlieb, C. Bara, J. U. Becker, V. Broecker
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  ABSTRACT: Renal function deteriorates in about half of patients undergoing other transplants. We report the results of 105 renal biopsies from 101 nonrenal transplant recipients (bone marrow 14, liver 41, lung 30, heart 20). Biopsy indications were protracted acute renal failure (9%), creatinine increases (83%), heavy proteinuria (22%), or renal insufficiency before re-transplantation (9%). Histological findings other than nonspecific chronic changes, hypertension-related damage, and signs of chronic CNI toxicity included primary glomerular disease (17%), mostly after liver transplantation (21%) or after bone marrow transplantation (29%), and thrombotic microangiopathy (TMA) namely (10%). TMA had the most serious impact on the clinical course. Besides severe hypertension, one TMA patient died of cerebral hemorrhage, 5 had hemolytic-uremic syndrome, and 6 rapidly developed end-stage renal failure. TMA patients had the shortest kidney survival post-biopsy and, together with patients with acute tubular injury, the shortest kidney and patient survival since transplantation. Nine TMA patients had received CNI, 3 of them concomitantly received an mTOR-inhibitor. CNI toxicity is implicated in most patients with renal failure after transplant of other organs and may play a role in the development of TMA, the most serious complication. However, decreased renal function should not be routinely ascribed to CNI.
  American Journal of Transplantation 09/2010; 10(9):2017-25. · 6.39 Impact Factor
• Article: [Fibrosing diseases.]

  H Haller, W L Gross
  Der Internist 01/2010; 51(1):5. · 0.30 Impact Factor
• Article: [Current problems of kidney transplantation].

  H Haller, N Richter, V Bröcker, W Gwinner, F Gueler, A Schwarz
  [show abstract] [hide abstract]
  ABSTRACT: The long-term problems after kidney transplantation have changed considerably in recent years. While formerly immunosuppression and prevention of acute rejection were of prime concern, now attention focuses on chronic alterations of the transplanted organ and long-term survival of the patients. The transplantation procedure itself has evolved into a standardized technique with a high level of surgical quality. Problems involving organ preservation and ischemia/reperfusion damage also play a role, especially in view of chronic aspects. Monitoring of long-term complications should follow a program for the transplanted organ as well as a program for the patient. Monitoring kidney function should address the organ more precisely than has previously been the case. Serum creatinine level and proteinuria alone provide insufficient information and only change long after cellular deterioration has begun. Hence it is imperative that new testing methods be developed. One possibility is offered by protocol biopsies that allow histological and molecular analysis of the kidney at regular intervals. The patient programs concentrate on diagnostics and treatment of the cardiovascular diseases. Furthermore, the patients must be screened for occurrence of neoplasia. There are no prospective studies covering all cardiovascular risk factors after kidney transplantation. This pertains particularly to the subject of hypertension.
  Der Internist 05/2009; 50(5):523-35. · 0.30 Impact Factor
• Article: Targeting the protein kinase C family in the diabetic kidney: lessons from analysis of mutant mice.

  M Meier, J Menne, H Haller
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  ABSTRACT: The protein kinase C (PKC) superfamily comprises proteins that are activated in response to various pathogenic stimuli in the diabetic state. Hyperglycaemia is the predominant stimulus that induces the activation of distinct PKC isoforms within a cell, each mediating specific functions, probably through differential subcellular localisation. The contribution of individual PKC isoforms can be directly addressed in vivo using innovative PKC-isoform-specific knockout (KO) mouse models, which are providing key insights into the physiological function of PKC isoform diversity in the development of diabetic nephropathy. Such studies can be a valuable complementary approach to more commonly used pharmacological analyses using agents such as ruboxistaurin mesylate (Arxxant, LY333531), which is claimed to specifically inhibit the PKC-beta-isoform. As expected given the multiple and specific properties of the isoforms in vitro, deletion of different PKC isoform signalling pathways leads to distinct phenotypes in mice. Notably, KOs of the individual PKCs assigned specific non-redundant biological functions to each isoform, which were not compensated for by the others. Thus, PKC isoform specificity and cellular diversity seem to be responsible for the divergent outcomes leading to albuminuria and/or renal fibrosis according to studies on the streptozotocin-induced mouse model of diabetes. This review discusses the role of individual PKC isoforms in diabetic nephropathy and their potential therapeutic implications. Defining and targeting mediators of increased intracellular activation in the diabetic microvasculature will have important clinical and therapeutic benefits and help in the design of novel effective therapies in the near future.
  Diabetologia 03/2009; 52(5):765-75. · 6.81 Impact Factor