[Nephrology for urologists]. / Nephrologie für Urologen.

By the very nature of things there are many overlaps between urology and nephrology. A close cooperation between the two disciplines is necessary for the benefit of the patient. From a nephrological perspective this article explains when and why participation of a nephrologist in treatment is recommended. In this context three essential points are explained: with respect to early recognition, renal hematuria, microalbuminuria, proteinuria, limited renal filtration function and glomerular filtration rate (GFR) are signs of renal disease; however, even patients with renal cysts should consult a nephrologist as early as possible due to the currently available treatment options. A delay in progression is possible and necessary for all chronic kidney diseases, independent of the trigger. Even when changes in the life style of the patient is troublesome and the adjustment of hypertension and hyperlipidemia sounds banal, their consistent implementation can result in a marked delay in the necessity for dialysis. The treatment of renal comorbidities is decisive and depends on the severity of the kidney disease. This includes the treatment of renal anemia, arterial hypertension, metabolic acidosis, uremic complications, electrolyte and water balance dysregulation and secondary hyperparathyroidism. By treating these comorbidities a marked reduction in the increased cardiovascular risk of nephrology patients can be achieved.

Improvement of renal graft function after conversion from a calcineurin inhibitor including immunosuppression to a mycophenolate sodium including regimen: a 4-year follow-up.

BACKGROUND: The most common immunosuppressive regimens after renal transplantation include calcineurin inhibitors (CNI). However, due to renal toxicity long-term graft survival does not seem to be positively affected by CNIs. METHODS: In the present study, we investigated 17 patients, in which the CNI immunosuppression was converted to a CNI-free, mycophenolate sodium (MPS) regimen. Conversion was performed due to progressive impairment of the graft function from suspected CNI toxicity. We retrospectively analyzed graft function as well as toxicity and surrogate markers for 4 years before and 4 years after conversion using a repeated-measures mixed model data analysis and/or a paired sample t-test. RESULTS: The mean time point of therapy conversion was 11.2 ± 4.6 years after transplantation. Within 1 month of CNI discontinuation, allograft function improved significantly, remaining at a significant level for 2 years. The estimated glomerular filtration rate increased from 43.4 ± 14.8 to a maximum of 55.7 ± 21.7 mL/min at 1 year after conversion (P = .0027). After 4 years, the end of the observation period, renal function was similar to the baseline. There were no significant side effects. CONCLUSION: These data suggested that, when chronic CNI-toxicity is suspected, renal allograft recipients may benefit from CNI withdrawal in favor of a MPS-including immunosuppressive regimen.

[Renal artery stenosis: angioplasty or drug treatment?]. / Nierenarterienstenose: Intervention oder medikamentöse Behandlung?

BACKGROUND AND OBJECTIVE: Angioplasty in patients with renal artery stenosis aims at reducing blood pressure and at improving kidney function. Its efficacy has however been questioned by recent published data. It was the aim of this retrospective study to compare angioplasty with medical treatment in an unselected patient population. METHODS: Data on 109 patients were retrospectively analysed. This cohort included all those patients admitted to the Lippe-Detmold Hospital between 1992 and 2008 for renal artery stenosis. The data included blood pressure, creatinine-based calculated glomerular filtration rate (cGFR), any renal dialysis, cardiovascular risk factors, events and survival time after transluminal renal angioplasty or drug treatment, respectively. RESULTS: Patients who had undergone angioplasty were younger (p = 0.04), had less cardiovascular co-morbidity (p < 0.01), but a higher degree of stenosis (p < 0.01). After a median follow-up of 32.5 (angioplasty) and 36.0 months (drug treatment), respectively, a significant decrease of cGFR was recorded in drug treated patients (- 16.2 ml/min, 95 %, CI - 25.7 to - 6.7) but not in the angioplasty group (- 4.5 ml/min, 95 %, CI - 13.5 to 4.5). There were no other significant differences were not observed. CONCLUSION: Younger patients with a high degree of renal artery stenosis but without generalized atherosclerosis more frequently underwent angioplasty in clinical practice. The smaller post-angioplasty reduction in the loss of renal function in this group needs to be validated in a prospective, randomized study.

Infliximab as therapeutic option in steroid-refractory ulcerative colitis after kidney transplantation: case report.

In inflammatory bowel disease refractory to established therapies, treatment with biological agents such as monoclonal tumor necrosis factor-α antibodies is an established therapeutic option. However, application in renal allograft recipients is either not licensed or has not yet been systematically examined. Herein, we present 2 case reports of renal allograft recipients who had steroid-refractory ulcerative colitis who demonstrated improvement of symptoms after treatment with infliximab, without signs of effect on transplant function. In both patients, stool frequency decreased significantly. Colonoscopy controls and histologic examination after initiation of treatment revealed a state of remission. Renal function parameters and drug concentrations remained constant.

The CX(3)C-chemokine fractalkine in kidney diseases.

The chemokine CX(3)C-L/FKN is expressed in both soluble and transmembrane/mucin hybrid forms, thus combining chemoattractant functions together with receptor/adhesion molecule properties. In contrast to other chemokine receptors, CX(3)C-R is expressed not only on lymphoid cell populations, but also on several intrinsic cells including tubular epithelial cells and renal fibroblasts where it regulates various aspects of cell viability, matrix synthesis and degradation, migration, inflammation as well as oxidative stress. In the kidney, the chemokines/receptor pair has been shown to play a role in nephrogenesis as well as in the pathogenesis primary and secondary nephropathies. In several animal models and human specimens with acute and chronic renal failure including allograft nephropathy, CX(3)C-L/CX(3)C-R has been shown to exert immune and non-immune mediated renal damages. A blockade of this chemokine system ameliorated acute and chronic renal damages, though the latter to a more robust extent. There seems to a role of the CX(3)C-L/CX(3)C-R pair in mediating acute renal inflammation as well as in progressive chronic renal failure. However, functional studies are lacking for many aspects and further studies are necessary to better define the functional properties of CX(3)C-L/FKN and its receptor.

[Microalbuminuria and albuminuria: differential diagnosis and consequences for treatment]. / Mikroalbuminurie und Albuminurie: Differenzialdiagnose und therapeutische Konsequenzen.

The occurrence of microalbuminuria or albuminuria indicates a disturbance of the barrier function of endothelial cells, basement membrane or of a structural-renal disease (including diseased podocytes). The prevalence of microalbuminuria in the general population is about 8 %, however, in high risk groups, prevalence rates of 50 % and more have been observed. Its incidence is strongly associated with increased cardiovascular morbidity and mortality. Blood pressure control and the blockade of the renin-angiotensin-aldosteron-system (RAAS), respectively, is the central mechanism to reduce cardio-vascular-renal end points as well as mortality.

Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium.

OBJECTIVE: Growth differentiation factor-5 (GDF-5), a member of the transforming growth factor (TGF)-beta family, is involved in joint development during embryogenesis and has the potential to regenerate cartilage in adult animals. As progression of chronic joint diseases is influenced by cytokines of the synovial tissue, we examined the expression and effects of GDF-5 in this tissue. METHODS: Microarray experiments were investigated for differential expression of GDF-5 in synovial tissues, synovial fibroblasts, and peripheral blood cells. GDF-5 expression was validated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, double immunofluorescence, and in situ hybridization in synovial tissue of normal donors (ND) and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of inflammation and therapy were investigated in RA and OA fibroblasts after stimulation with interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, methotrexate (MTX), and prednisolone. The influence of GDF-5 on macrophages was studied by chemotaxis assay. RESULTS: Microarray analysis and immunostaining revealed expression predominantly in synovial fibroblasts. Compared to patients without immunomodulating drugs, expression of GDF-5 was decreased significantly in patients receiving glucocorticoids and/or disease-modifying antirheumatic drugs (DMARDs) (p = 0.007), but did not differ between the total group of ND, OA, and RA. Stimulation with prednisolone and TNFalpha reduced GDF-5 expression in OA and RA fibroblasts, whereas MTX and IL-1beta revealed minor or no relevant change. GDF-5 also reduced cell migration of macrophages (p<0.001). CONCLUSION: GDF-5 is expressed in synovial fibroblasts and may counteract macrophage infiltration. Its modulation by inflammation and therapy suggests that glucocorticoids play a conflicting role by suppressing not only inflammation but also putative mechanisms of repair.

[Recent examples for drug (developments) in primary, secondary and tertiary prevention]. / Aktuelle Beispiele für Arzneimittel (-entwicklungen) in der primären, sekundären und tertiären Prävention.

The prevention of disease and the prevention of subsequent disease is one of the main themes in public health as well as in clinical medicine. Besides targeted interventions aiming at the total population (public health) individual steps like life style intervention and use of pharmacotherapy are important components. Taking acute myocardial infarction as an example it is illustrated, how risk factors can be targeted and which new drugs in development have been either just registered or are in late phase III of clinical testing shortly before registration and final approval. In this context it was shown that there are many exciting new options to reduce risk factors. On the other hand there are indications in which new drug development is likely not to contribute to an improvement of the situation (e. g. arterial hypertension) and in which further targeted intervention aiming at physicians (therapeutic pathways, guidelines, point of care research) and patients (life style intervention, compliance) has to be undertaken to improve the efficacy of currently available pharmacotherapy.

Effective treatment of hepatitis C-associated immune-complex nephritis with cryoprecipitate apheresis and antiviral therapy.

A 38-year-old pregnant woman (19th week of pregnancy) complained of fatigue, cold inducible paresthesias, generalized edema and mild arterial hypertension. Her past medical history was notable for frequent episodes of polyarthralgia and positivity for rheumatoid factor. On admission, acanthocyturia and unselective glomerular-tubular proteinuria with 19 g/d were detected with a slight decrease in creatinine clearance. Rheumatoid factor was robustly elevated and a cryocrit of 1.5 vol%, caused by a so far unknown replicative hepatitis C, was detected. Renal biopsy yielded membrano-proliferative glomerulonephritis. During pregnancy, high-dose corticosteroid therapy was administered. Edema disappeared and blood pressure normalized under albumin substitution and low-dose furosemide application. However, Cesarian section became necessary due to placental insufficiency at 27 weeks of gestation. Thereafter, neither virus load, cryocrit nor proteinuria decreased significantly under a combined therapy with pegylated interferon-a and ribavirin. Thus, cryoprecipitate apheresis was initiated resulting in robust decreases of clinical complaints, viral load, cryocrit and proteinuria. Cryoglobulinemia with renal involvement caused by hepatitis C is difficult to treat due to limitations of immunosuppressive and anti-viral therapy. In our patient, cryoprecipitate apheresis was a safe and effective therapeutic addition to standard therapy.

Bioimpedance analysis and intradialytic hypotension in intermittent hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is one of the most severe complications during hemodialysis. Its appearance is caused in part by rapid fluid removal with concomitant failure in blood pressure regulation but also by other dialytic-dependent and independent factors. PATIENTS AND METHODS: We investigated total (TBW), extracellular (ECW) and intracellular water (ICW) in chronic intermittent hemodialysis dialysis hypotension-prone (CRF-HP, n = 11) and nonhypotension-prone (CRF-NHP, n = 10) patients with end-stage renal disease before, every 30 minutes during, as well as after dialysis and within onset of intradialytic hypotension by multifrequent bioimpedance analysis (BIA). Additionally, intradialytic time course of BIA in patients with acute renal failure (ARF) and septic shock (n = 10) was observed. RESULTS: IDH occurred in 72.1% of CRF-HP and in 80% of ARF patients. In CRF-HP and CRF-NHP, ECW significantly decreased by -12.44 +/- 4.22% in CRF-HP and -9.0 +/- 6.2% in CRF-NHP comparing pre- and post-dialysis values (each p < 0.01). Conversely, ICW increased by +11.5 +/- 11.3% in CRF-HP and +18.4 +/- 25.2% in CRF-NHP (each p < 0.05). In patients with ARF no significant changes could be detected. Calculated ECW/ICW and ECW/TBW ratio significantly decreased in CRF patients with a higher rate in CRF-HP patients (p < 0.05). Neither ECW/ICW nor ECW/TBW ratio correlated with mean arterial pressure. The onset of intradialytic hypotension (n = 35) did not differ intraindividually compared to normotensive periods (n = 411). Fluid removal in CRF patients seems to be mainly from the extracellular space. The reduced decreases in ECW/ICW and ECW/TBW ratios in CRF-HP compared to CRF-NHP may indicate an insufficient refilling from intra- to extracellular compartment in CRF-HP. CONCLUSION: In conclusion, multifrequent BIA is not capable to predict hypotension in the individual patient during a particular dialysis session.

[Bone morphogenetic proteins in the skeletal system]. / Bone Morphogenetic Proteins im Skelettsystem -- eine zusammenfassende Darstellung.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta superfamily. Their potential for organ and tissue regeneration and repair has been intensively investigated in recent years. Studies on fetal development have demonstrated the important role of these proteins for the development and differentiation of different organs. Miss-expression or mutation of BMPs may lead to severe abnormalities or even abortion. However, a regenerative potential has also been recognized for the adult organism. BMPs support fracture healing and may contribute to treatment of joint diseases. Thus, BMP-7 is one of the first BMPs approved for clinical application in non-unions of bone fractures resistant to conventional therapy. In degenerative and inflammatory joint diseases, experimental data suggest a decrease of BMP expression in cartilage tissue. Therefore, BMPs could be promising therapeutic candidates in these diseases, although more detailed analyses are necessary. In this review we will focus on bone morphogenetic proteins and discuss present and putative future clinical applications.

Differentiation of M1 myeloid precursor cells into macrophages results in binding and infection by Theiler's murine encephalomyelitis virus and apoptosis.

Infection of susceptible mouse strains with BeAn, a less virulent strain of Theiler's murine encephalomyelitis virus (TMEV), results in immune system-mediated demyelinating lesions in the central nervous system (CNS) similar to those in multiple sclerosis. Since macrophages appear to carry the major detectable antigen burden in vivo, and purification of sufficient cell numbers from the CNS for detailed analysis is difficult, macrophage-like cell lines provide an accessible system with which to study virus-macrophage interactions. The myeloid precursor cell line M1 differentiates in response to cytokines and expresses many characteristics of tissue macrophages. Incubation of TMEV with undifferentiated M1 cells produced neither infection nor apoptosis, whereas differentiated M1 (M1-D) cells developed a restricted virus infection and changes indicative of apoptosis. Virus binding and RNA replication as well as cellular production of alpha/beta interferons increased with differentiation. Although the amount of infectious virus was highly restricted, BeAn-infected M1-D cells synthesized and appropriately processed virus capsid proteins at levels comparable to those for permissive BHK-21 cells. Analysis of Bcl-2 protein family expression in undifferentiated and differentiated cells suggests that susceptibility of M1-D cells to apoptosis may be controlled, in part, by expression of the proapoptotic alpha isoform of Bax and Bak. These data suggest that macrophage differentiation plays a role in susceptibility to TMEV infection and apoptosis.

Pronounced renal vasoconstriction and systemic hypertension in renal transplant patients treated with cyclosporin A versus FK 506.

This prospective study investigated hypertension and renal vasoconstriction developing during the 1st year after renal transplantation in patients randomly allocated to treatment with FK 506 (n = 28) or CyA (n = 13). Starting doses were 0.2-0.3 mg/kg per day for FK 506 and 5-8 mg/kg per day for CyA: doses were subsequently adjusted to trough levels (5-15 ng/ml for FK 506 and 100-150 ng/ml for CyA). We compared 24-h ambulatory blood pressure measurement, antihypertensive treatment, serum creatinine, and resistance index (RI), measured by Doppler ultrasound at the level of the interlobar artery. Until month 2 of treatment, FK 506-treated patients had a significantly lower RI (8%) and better renal graft function, as evidenced by significantly lower serum creatinine values. Some 13% of FK 506-treated patients, compared to 70% of CyA-treated patients (P < 0.01), needed additional antihypertensive drugs after transplantation to keep blood pressure stable. FK 506 treatment, at the above-mentioned dosages, was associated with a significantly higher number of infections (urinary tract infection, pyelonephritis, and pneumonia). We conclude that CyA produces greater renal vasoconstriction and systemic hypertension than FK 506, as reflected in higher renal interlobar artery RI values and a greater need for antihypertensive treatment. After 2 months of treatment and a reduction in CyA trough levels, the renal effects (i.e., lower RI and lower creatinine values), but not the systemic hypertensive effects, disappear.