Spiegelmer Inhibition of MCP-1/CCR2--Potential as an Adjunct Immunosuppressive Therapy in Transplantation.

The rejection process remains the key unsolved issue after transplantation of disparate tissue. The CC chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) has been reported to be involved in the process of alloimmune interaction. Spiegelmers are l-oligonucleotides that can be designed to bind to pharmacologically relevant target molecules. Here, we tested a high-affinity Spiegelmer-based MCP-1 inhibitor (mNOX-E36) in an allogeneic heart transplant model. Fully vascularized allogeneic heterotopic heart transplantations from BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti-MCP-1-Spiegelmer (mNOX-E36) in monotherapy or in combination with subtherapeutic doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received equivalent doses of a non-functional Spiegelmer (revmNOX-E36). Graft survival of allogeneic heart transplants was slightly but significantly prolonged under mNOX-E36 monotherapy (median graft survival 10 day ± 0.7) compared to revmNOX-E36 (median graft survival 7 day ± 0.3; P = 0.001). A synergistic beneficial effect could be seen when mNOX-E36 was administered in combination with subtherapeutic doses of CsA (18 day ± 2.8 versus 7 day ± 0.3; P < 0.0001). Levels of inflammatory cytokines and 'alarmins' were significantly reduced, and the number of F4/80(+) cells was lower under combination therapy (1.8% ± 1.3%; versus 14.6% ± 4.4%; P = 0.0002). This novel inhibitor of the MCP-1/CCR2 axis (mNOX-E36), which has already proven efficacy and tolerability in early clinical trials, alleviates acute rejection processes in allogeneic transplantation especially when combined with subtherapeutic doses of CsA. Thus, mNOX-E36 may have potential as an adjunct immunomodulatory agent.

CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results.

OBJECTIVES: To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. METHODS: Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. RESULTS: Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CONCLUSION: CT perfusion of kidney allografts may help to differentiate between ATN and rejection. KEY POINTS: • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.

The source matters: no impact of the CCL2/MCP-1-1-2518G polymorphism of the donor on renal allograft outcome during the first year after transplantation.

Chemokines are involved in the recruitment of inflammatory cells to vascularized allografts. The chemokine CCL2/MCP-1 is expressed during allograft dysfunction, which is associated with the recruitment of inflammatory cells. Both intrinsic renal cells (donor origin) as well as infiltrating inflammatory cells (recipient origin) can be a source of CCL2/MCP-1. We previously demonstrated that the recipient MCP-1-2518G polymorphism is associated with increased CCL2/MCP-1 production by inflammatory cells and decreased renal allograft survival. We evaluated the impact of the MCP-1-2518G polymorphism in donor cells on renal allograft outcomes. We enrolled 252 recipients of kidney allografts in this retrospective study who had received grafts from 152 cadaveric donors. The CCL2/MCP-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. Outcome parameters studied were acute biopsy proven rejection (Banff criteria), serum creatinine, and glomerular filtration rate (GFR) at 1 year after transplantation, allograft loss, and death. MCP-1-2518 genotypes were in HW equilibrium. A/A was present in 125 (49.6%), A/G in 107 (42.5%), and G/G in 20 (7.9%) donor kidneys. There were no significant differences in the number of rejection episodes, the number of allograft losses, serum creatinine, GFR, or overall survival 1 year after transplantation. In contrast with the detrimental effect of the CCL2/MCP-1 polymorphism of the recipient, the CCL2/MCP-1 polymorphism of the donor has no impact on the allograft outcome during the first year after transplantation. The impact on the long-term outcomes needs further evaluation.

Contrast-enhanced ultrasound (CEUS) as a new technique to characterize suspected renal transplant malignancies in renal transplant patients in comparison to standard imaging modalities.

BACKGROUND: Renal transplant patients have a higher risk for malignancies of the renal transplant. In most cases suspected renal malignancies will be detected during the regular ultrasound follow-up and will require cross-sectional imaging to rule out a malignant aetiology. But it is well known that contrast agents for computed tomography or magnetic resonance imaging are critical in patients with limited renal function. OBJECTIVE: This study aims to compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and gold standard imaging modalities in characterizing suspected renal transplant malignancies in renal transplant patients. METHODS: A total of 22 renal transplant patients who underwent one or more CEUS examinations and at least one standard imaging modality (CT or MRI) between 2005 and 2017 were included. Patient ages ranged from 28.2 years to 74.6 (mean age 55.7 years; SD±13.0 years). CEUS of 22 patients was correlated with a standard imaging modality, CT (15 out of 22) or MRI (7 out of 22), serving as gold standard. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 94.4%, a positive predictive value (PPV) of 80%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is an eligible method to help characterizing suspected renal malignancies in renal transplant patients compared to the well-established imaging modalities CT and MRI. As an imaging modality with no nephrotoxic effects CEUS can be used repeatedly even in patients with limited renal function.

Vascular rejection in renal transplant: Diagnostic value of contrast-enhanced ultrasound (CEUS) compared to biopsy.

BACKGROUND: Despite of the more potent immunosuppressive medication, vascular rejection is still a major issue after renal transplantation. Renal biopsy is the gold standard diagnostic to evaluate acute and chronic allograft rejection. As it is an invasive diagnostic there is the risk of complications like haematoma, arteriovenous fistulas, active bleeding or infection. Contrast-enhanced ultrasound is a non-invasive imaging modality that allows visualising renal transplant perfusion. OBJECTIVE: To analyse the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) compared to biopsy as gold standard in diagnosing vascular rejection in renal transplant patients. METHODS: A total of 57 renal transplant recipients with poor renal allograft function with initial diagnostic imaging between 2006 and 2017 were included in the study. Clinical data and imaging studies were analysed retrospectively. The diagnostic accuracy of CEUS in diagnosing vascular rejection of the renal transplant was compared to renal biopsy as gold standard. Out of 57 patients 7 patients showed signs of vascular rejection in biopsy. In 6 out of these 7 patients CEUS described irregularities in renal perfusion suspicious of vascular rejection. RESULTS: CEUS showed a sensitivity of 85.7%, a specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 98.0%. CONCLUSIONS: CEUS is a safe, non-nephrotoxic imaging modality for the initial imaging of renal transplant recipients with elevated kidney function parameters suspicious of vascular rejection. Compared to renal biopsy as gold standard CEUS shows a high specificity and PPV in detecting signs of vascular rejection. Since sub-types of vascular rejection with cellular and humoral components with greater risk for allograft loss have been described renal biopsy is inevitable in these cases.

Five-year follow-up after late conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction.

BACKGROUND: Chronic allograft nephropathy (CAN) is, among others, caused by nephrotoxic side effects of calcineurin inhibitors (CNI), which are to date still the mainstay of immunosuppressive therapy. Sirolimus (SIR), an immunosuppressive compound without effects on glomerular perfusion, has been used in CNI-sparing immunosuppressive protocols. We report the 5-year follow-up of a prospective, controlled conversion study from CNI to SIR in patients with moderately to severely impaired renal function. METHODS: Twelve renal transplant recipients with moderately to severely impaired renal function (estimated glomerular filtration rate of 17 to 35 mL/min according to the MDRD formula), enrolled in a prospective, controlled 1-year pilot study were followed for 5 years. RESULTS: Three renal grafts (25%) were lost during the 5-year follow-up. Graft loss was due to noncompliance in one patient and to CAN in the other two patients. These two patients returned to dialysis 43 and 59 months after conversion, corresponding to 86 and 75 months after transplantation, respectively. Six of nine patients had a stable or even better renal function compared to the baseline. The lipid profile increased initially, but then remained stable over time. CONCLUSION: Conversion of immunosuppressive therapy from CNI to SIR in patients with impaired renal function more than 1 year after transplantation is feasible and safe yielding improved renal function in the majority of patients, which was sustained at 5 years follow-up.

The diagnostic value of contrast-enhanced ultrasound (CEUS) as a new technique for imaging of vascular complications in renal transplants compared to standard imaging modalities.

BACKGROUND: Vascular complications in renal transplant patients are a well-known issue in post transplant patient care. If malfunctioning of the renal transplant is suspected to be caused by vascular complications an early diagnosis and therapy is required to maintain the renal transplant. Computed tomography (CT), digital substraction angiography (DSA) and radioisotope renography are the gold standard imaging modalities to diagnose vascular complications. OBJECTIVE: To analyse the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) in comparison to the standard imaging modalities CT, DSA and radioisotope renography in the diagnosis of vascular complications in renal transplant patients. METHODS: A total of 33 renal transplant recipients with elevated kidney function parameters with initial diagnostic imaging between 2006 and 2017 were included in the study. The imaging studies and clinical data were analysed retrospectively. The diagnostic accuracy of CEUS was compared to CT, DSA and renal scintigraphy respectively which are classified as gold standard for diagnosis of vascular complications in renal transplant patients. Out of 23 patients 15 patients showed vascular complications in CT, DSA or radioisotope renography and in 15 out of 15 patients CEUS detected the vascular complication. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 66.7%, a positive predictive value (PPV) of 71.4%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is a non-nephrotoxic and safe method for the initial imaging of vascular complications in renal transplant recipients. Compared to the gold standard imaging modalities CT, DSA and radioisotope renography CEUS shows a high sensitivity and NPV in detecting vascular complications. In cases with suspected stenosis of the transplant renal artery additional DSA might be needed.

HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy.

Renal disease is becoming an increasingly prevalent entity in human immunodeficiency virus (HIV)-infected patients; it occurs in a variety of clinical settings and is associated with histopathological changes. HIV-related renal impairment can present as acute or chronic kidney disease; it can be caused directly or indirectly by HIV and/or by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Acute renal failure is frequently caused by the toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances used in the treatment of opportunistic infections. Chronic renal disease can be caused by multiple pathophysiological mechanisms, leading to HIV-associated nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic microangiopathy, and various forms of immune complex glomerulonephritis. The increase in life expectancy and alteration of lipid metabolism due to receipt of highly active antiretroviral therapy are expected to result in an increased prevalence of diabetes and hypertension and, thus, to secondary diabetic and hypertensive renal damage. Antiretroviral agents, such as indinavir and tenofovir, have been associated with nephrotoxic drug effects that have been shown to be reversible in most cases. In this article, we review the current knowledge about acute and chronic HIV-associated renal disease, metabolic alterations and related nephropathies, and toxic drug effects of combination antiretroviral pharmacotherapy.

Conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction.

BACKGROUND: Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction. METHODS: Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld. RESULTS: One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7). CONCLUSION: Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.

Renal effects of gadopentetate dimeglumine in patients with normal and impaired renal function.

Gadolinium chelates are widely used in magnetic resonance imaging as contrast medium in patients with nephropathy. However, only few studies have investigated the effect of gadolinium on serum creatinine concentration and estimated GFR as surrogate markers of renal function. This study was performed to evaluate the effect of gadopentetate dimeglumine in a dose sufficient for diagnostic and interventional purposes on renal function in a large sample of patients. We analyzed serum creatinine and serum-urea levels before and after the administration of gadopentetate dimeglumine in patients with normal and patients with pre-existing impaired renal function. Age, height, body mass, sex, medication and preexisting illnesses such as diabetes, renal artery stenosis and heart disease were monitored. In 181 patients with normal renal function, there was no statistically significant change in serum creatinine concentration after the administration of gadopentetate dimeglumine (at baseline: 0.72 +/- 0.18 mg/dl, after gadolinium: 0.73 +/- 0.22 mg/dl). In contrary, serum creatinine levels decreased significantly after the administration of gadolinium in 198 patients with pre-existing renal impairment (1.82 +/- 1.03 mg/dl before and 1.72 +/- 1.03 mg/dl after gadolinium) (p < 0.01). According to this surrogate marker of renal function, the change of estimated GFR in patients with normal baseline renal function was not significant, while in patients with impaired renal function, GFR increased after the administration of gadolinium (p < 0.001). The high diagnostic value of gadolinium contrast media is associated with a very small risk of adverse reactions. Our findings show that the administration of gadolinium even is associated with a decrease of serum creatinine in patients with pre-existing renal impairment. In conclusion, the use of gadolinium-based contrast media may be considered as a safe alternative in patients with impaired renal function for whom use of iodine-based contrast agents is prone to a high rate of radiocontrast-induced nephropathy.

Low sodium and furosemide-induced stimulation of the renin system in man is mediated by cyclooxygenase 2.

The aim of this study was to examine the effects of highly selective inhibition of cyclooxygenase 2 (COX-2) with rofecoxib on the renin system during long-term stimulation and after short-term stimulation. Six healthy male volunteers received, in a randomized crossover design, a low-sodium diet for days 1 through 9 with or without 25 mg rofecoxib twice daily on days 5 through 9 and, in addition, 20 mg of furosemide intravenously on day 8. Plasma renin activity increased 2 to 3 times over baseline with a low-sodium diet and 5 times over baseline 30 minutes after intravenous furosemide; it was still elevated nearly 5 times on day 9. These effects were completely blocked by rofecoxib. Plasma aldosterone and urinary aldosterone concentrations basically reflected the findings with plasma renin activity. Urinary sodium excretion decreased during a low-sodium diet and increased after intravenous furosemide without being significantly affected by rofecoxib. We have concluded that low-sodium and furosemide-stimulated renin and aldosterone secretion is completely blocked in healthy volunteers during COX-2 inhibition with rofecoxib, suggesting that intact COX-2 is of major importance for stimulation of the renin system under these conditions in man.

Renal transplantation in a patient with end stage renal disease due to cholesterol embolism.

BACKGROUND: Renal failure due to cholesterol emboli is mostly irreversible. Therefore chronic renal replacement therapy is necessary. However, to the best of our knowledge no published experience exists with renal transplantation in patients with end-stage renal disease (ESRD) due to cholesterol embolization (CE). METHODS: Renal transplantation was performed in a 64-year-old man who suffered from ESRD due to CE after coronary angiography. Because our patient presented with a typical profile of cardiovascular risk factors effective long-term control of these risk factors before and after transplantation was a mandatory prerequisite before considering transplantation. RESULTS: After one rejection episode serum creatinine values have been stable and no major complications have occurred during a follow-up of 18 months. No signs of recurrent cholesterol emboli into the donated kidney were seen in renal biopsies performed due to graft rejection. CONCLUSION: Cholesterol embolization is an uncommon reason for ESRD and mainly occurs after invasive vascular procedures in patients with hyperlipidemia, arterial hypertension, and smoking. Because ESRD due to CE often is irreversible, chronic renal replacement therapy may be necessary. As demonstrated in our report, renal transplantation should be considered. However, in this setting effective long-term control of the underlying risk factors before and after renal transplantation has to be ensured.

Early loss of renal transplants in patients with thrombophilia.

BACKGROUND: We considered the possibility that thrombophilia may propagate graft thrombosis and therefore we evaluated the protein C system, which is a natural anticoagulant. Potential alterations in this system include protein C or protein S deficiency, inhibition through a lupus anticoagulant (LA), or a resistance to activated protein C due to the factor V Leiden (FVL) mutation. METHODS: One hundred thirty-two consecutive renal transplant patients, not known to have abnormal thrombostasis, in whom 1-year graft survival could be assessed, underwent laboratory testing for protein C or S activity, LA, and FVL. Transplant survival and demographic data were extracted from the hospital record. RESULTS: We identified 18 patients with thrombophilia (FVL, 10; LA, 6; protein S, 2) who had received a total of 28 renal transplants. Of these 28 transplant recipients, 11 transplants were lost within the first year, compared with 21 of 155 transplants to 114 patients without thrombophilia (P=0.0003). Median graft survival for patients with thrombophilia was 30 months (range: 0 to 166), compared with 86 months (range: 0 to 212) for patients without thrombophilia (P<0.01). The presence of thrombophilia represented a 3.5-fold (95% confidence interval, 2.3-5.3-fold) risk for 1-year graft loss. CONCLUSION: In this retrospective study, patients with thrombophilia had a significantly higher risk of early transplant failure. These data point toward a potential contribution of thrombophilia to transplant loss, a hypothesis that needs further study.

Increased rate of renal transplant failure in patients with the G20210A mutation of the prothrombin gene.

In patients with thrombophilia caused by reduced physiological anticoagulation, renal transplant failure occurs more frequently. Previous studies showed the importance of the protein C system, a physiological anticoagulatory pathway that inhibits thrombus formation. However, excess activation of the hemostatic system also may result in thrombosis. The G20210A mutation in the prothrombin gene is such a prothrombotic risk factor that results in increased thrombus formation because of elevated factor II levels in plasma. We analyzed graft function in 270 consecutive patients who received 311 renal transplants. The presence of a normal or mutated prothrombin allele was determined by polymerase chain reaction amplification and restriction fragment length polymorphism analysis of genomic DNA. Demographic data were extracted from hospital records. Graft survival was calculated for patients with and without the G20210A mutation. We identified 9 patients heterozygous for the G20210A mutation in the prothrombin gene who had received a total of 12 renal transplants. Of these 12 transplants, 2 grafts were lost within the first year. Median graft survival for patients heterozygous for the 20210A allele was 65.9 months (range, 0 to 101 months) compared with 149 months (range, 0 to 237 months) for patients homozygous for the normal 20210 G allele (P = 0.02). The G20210A mutation represented a 2.95-fold (95% confidence interval, 1.03 to 8.46) increase in risk for graft loss. Only 1 patient with this mutation achieved graft function exceeding 101 months. The G20210A mutation of the prothrombin gene is an independent risk factor for graft failure.

Therapeutic strategies in the prevention of acute renal failure.

The current management of acute renal failure rests largely on the avoidance of ischemic and nephrotoxic insults, attention to fluid and electrolyte balance, and the use of dialytic procedures when necessary. The efficacy of several strategies in experimental renal disease, reviewed in this article, raises the possibility that available to the clinician in the not-too-distant future would be analogous interventions that interrupt pathways of tissue injury and/or summon processes that attenuate the damaging effect of a given insult. The implementation of such therapeutic modalities would expand the management of acute renal failure from its current conservative approach to one encompassing therapeutic interventions that potentially prevent the occurrence of acute renal failure. Moreover, the remarkable and ever-increasing understanding of acute renal failure, in all its deranged cell biology and complex pathogenesis, offers the promise of discerning still better and more effective therapeutic interventions.

Evaluation of atherosclerosis in patients with central retinal vein occlusion by carotid artery duplex scanning and echocardiography: a prospective case-control study.

BACKGROUND AND PURPOSE: Central retinal vein occlusion (CRVO) is a common cause of retinal vascular visual loss second to diabetic retinopathy. Atherosclerotic risk factors are thought to affect vascular flow or cause retinal vascular wall abnormalities, thereby contributing to development of CRVO. Previous studies did not fully evaluate the degree of atherosclerotic disease. The purpose of this study was to determine the degree of atherosclerosis of the carotid artery by duplex scanning and to investigate cardiac manifestations of atherosclerotic risk factors by echocardiography in patients with CRVO. MATERIAL AND METHODS: 39 patients (age 63.1 years [50-84 years], 21 men, 18 women) with CRVO were compared with a control group consisting of 39 individuals (age 59.3 years [49-81 years], 19 men, 20 women) in whom echocardiography was performed to rule out endocarditis. Clinical examination, laboratory testing, carotid artery duplex scanning and echocardiography were performed in all patients. RESULTS: Echocardiography revealed significantly increased prevalence of left ventricular hypertrophy (30.8% in CRVO patients, 5.1% in controls) as a typical sign of hypertensive heart disease in CRVO patients, which is consistent with the increased prevalence of hypertension (HTN) (46.2% in CRVO patients, 15.4% in controls). The prevalence of atherosclerosis of carotid artery and ascending aorta, and all other echocardiographic findings were comparable in CRVO patients and controls: regional wall motion abnormality, left ventricular dilatation, aortic valve calcification, and mitral valve calcification. CONCLUSION: Our study demonstrates that CRVO is not associated with atherosclerosis of large arteries, such as the carotid artery and the ascending aorta. We propose that the retinal artery atherosclerosis seen in most CRVO patients is caused by HTN.

Quantitative gene expression analysis of fractalkine using laser microdissection in biopsies from kidney allografts with acute rejection.

Percutaneous biopsy of the kidney remains the gold standard to establish a diagnosis in renal diseases. Only semiquantitative assessments of gene expression on biopsies have been possible so far. We studied gene expression of the chemokine fractalkine (FKN) in 12 biopsies from laser microdissected kidney allografts that showed histologic signs of acute rejection and 10 controls. As quantified by real-time PCR, the relative tubular FKN expression increased from 1.0 [0.81 to 2.95] (median [range]) in controls to 12.44 [0.90 to 191.0] in acute rejection (P < .01); glomerular FKN expression from 1.3 [0.07 to 27.44] to 12.22 [1.32 to 50.23] (P < .05); and vascular expression, from 0.72 [0.37 to 5.11] to 7.07 [1.19 to 73.49] (P < .01). Furthermore, there was a trend toward higher glomerular FKN expression among patients with more severe rejection. Our results suggest a role of FKN in acute renal allograft rejection.

[48-year old woman with diffuse pulmonary calcifications after allogeneic kidney transplantation. A rare manifestation of tertiary hyperparathyroidism]. / 48-jährige Patientin mit ausgedehnten pulmonalen Verkalkungen nach allogener Nierentransplantation. Seltene Manifestation eines tertiären Hyperparathyreoidismus.

HISTORY: A 48-year-old woman was hospitalized because of the presence of asymptomatic bilateral pulmonary infiltrates in the conventional chest radiograph. An antibiotic treatment administered 3 months before had been without any effect on the radiological aspect. The patient had had an end-stage renal disease of unknown cause and was on hemodialysis since 1993. 1997 she received a cadaveric renal transplant. INVESTIGATIONS: Computed tomography scan detected the infiltrates as diffuse calcifications mainly at the lung bases. Extended arterial vascular calcifications were also found. Since approximately 4 years calcium-phosphorus product and parathyroid hormone had been increased. TREATMENT AND COURSE: Because of the long-term increased calcium-phosphorus product and the high parathyroid hormone levels we interpreted the pulmonary calcifications as a result of the tertiary hyperparathyroidism. After parathyroidectomy calcium-phosphorus product and PTH levels normalized, but our patient suffered from increasing disturbances of the peripheral blood circulation induced by the vascular calcifications, necessitating amputation of finger and toe tips. CONCLUSION: Patients with renal failure should undergo regular controls of calcium, phosphorus and parathyroid hormone when creatinine clearance is below 50 ml/min/1.73 m2. Only an early medical treatment can prevent the various complications induced by the secondary or tertiary hyperparathyroidism. If medical therapy fails, parathyroidectomy has to be done. Especially before renal transplantation the extent of hyperparathyroidism has to be carefully analyzed and treated aggressively, if necessary by surgery before the date of transplantation.

[Hematuria and nephritic sediment]. / Marathonlauf, Nephritis oder Harnwegsinfekt? Wie Sie Blut im Urin rationell abklären.

Vigorous physical exercise is just as likely to be the cause of hematuria as are diseases of the efferent urinary tract, inflammatory renal disease or tumors. The microscopic search for dysmorphic erythrocytes (acanthocytes), casts or leukocytes in the sediment is a helpful technique for deciding the how to proceed with further diagnostic measures. Morphological changes in more than 17% of the erythrocytes are highly suggestive of a glomerular cause, Also, the presence of various casts points to kidney disease. The typical microscopic picture of interstitial nephritis is sterile leukocytosis. This may be of atheroembolic origin, medication-induced, or viral. In any case, the nephritic sediment should be clinically evaluated only in the context of further information such as the patient's age, comorbidities, or medication.

[Problems with the follow-up and aftercare of transplanted patients exemplified by kidney transplantation]. / Transplantationspatienten brauchen kompetente Nachsorge. Welche Hürden Ihr Patient jetzt nehmen muss.

The large number of post-transplantation patients overwhelm the capacity of most transplantation centers (TC) to provide aftercare, with the result that close cooperation has been established between transplantation centers and ambulatory centers. Surveillance of immunosuppression, but also the treatment of concomitant cardiovascular diseases and the elevated tumorigenesis rate in transplanted patients, presuppose a high degree of readiness to undergo further education on a permanent basis. Furthermore, patient compliance is a factor of decisive importance for ensuring optimal care by the general physician. In close cooperation with the TC, the latter bears a considerable burden of responsibility for the lifelong aftercare of such patients.