The Kolff-Merrill artificial kidney; clinical application in acute renal insufficiency

Acute renal insufficiency is often called "lower nephron nephrosis." Its recognition, its prognostic significance, and its therapy by conservative measures are receiving increasing clinical emphasis. The mortality rate in this complicated syndrome still remains unduly high. One method of therapy of anuric patients whose lives are in jeopardy because of fulminating uremia or critical potassium intoxication is use of an artificial kidney to "purify" the blood stream by means of extracorporeal dialysis.The author describes clinical (and laboratory) experience with ten such dialyzed patients, eight of whom presented the classical picture of acute renal insufficiency. Four died, one from unrecognized coronary occlusion, another from antecedent, overwhelming peritonitis. Two other patients with chronic kidney disorders received no benefit from dialysis and died of renal disease. Good biochemical and clinical response was brought about in six cases of lower nephron nephrosis. Presumably, these six patients would have died had they not been subjected to artificial dialysis.     

Use of the artificial kidney; its place in the treatment of acute renal failure

Of 57 patients with severe, but potentially reversible, acute renal failure who were observed during a recent four-year period, some had dialysis with an artificial kidney and some did not. Twenty survived with the standard "conservative" management alone; 19 survived with a combination of "conservative" and "intensive" (that is, artificial kidney) treatment; 18 patients died. One error that was made in the management of all 18 patients who died, was excessive delay in the use of the artificial kidney. Hemodialysis should be used whenever serious electrolyte abnormality exists, whenever the blood urea nitrogen exceeds 150 mg. per 100 cc. or whenever clinical signs of uremia first appear. One or more of these indications will usually, but not always, become evident between the fifth and the eighth day of virtual anuria.     

USE OF THE ARTIFICIAL KIDNEY—Its Place in the Treatment of Acute Renal Failure

Of 57 patients with severe, but potentially reversible, acute renal failure who were observed during a recent four-year period, some had dialysis with an artificial kidney and some did not.Twenty survived with the standard “conservative” management alone; 19 survived with a combination of “conservative” and “intensive” (that is, artificial kidney) treatment; 18 patients died.One error that was made in the management of all 18 patients who died, was excessive delay in the use of the artificial kidney.Hemodialysis should be used whenever serious electrolyte abnormality exists, whenever the blood urea nitrogen exceeds 150 mg. per 100 cc. or whenever clinical signs of uremia first appear. One or more of these indications will usually, but not always, become evident between the fifth and the eighth day of virtual anuria.     

A Clinical Evaluation of Peritoneal Dialysis

A total of 18 peritoneal dialyses were performed on 14 patients at the Hamilton Civic Hospital over a period of 11 months. Nine of these patients were in uremia, four had non-nephrotoxic intoxication, and one had hepatic coma. Patients with chronic uremia may present with acute renal failure which may be treated by peritoneal dialysis with resultant significant prolongation of life. A decreased mortality rate might be expected in acute renal failure if dialysis is implemented before the classical picture of uremia develops. Many non-nephrotoxic intoxicating substances are readily dialysable. Considerable benefit to the patient and decreased time in hospital may result from the use of this procedure in cases of intoxication with such substances. Peritoneal dialysis may be of value in treatment of intractable congestive heart failure. This procedure may eventually provide another means of treating hepatic coma.     

Free tissue transfer in patients with renal disease

Several authors have cited renal disease as a risk factor for free flap failure. The authors performed a retrospective analysis of all patients who underwent free tissue transfer with concomitant renal disease, including acute renal failure, end-stage renal disease, chronic renal insufficiency, and functional kidney transplants, to determine what effect renal disease has on flap survival and overall reconstructive outcome. More than 1053 free flaps were examined. Renal disease was identified in 32 patients who underwent 33 free tissue transfers. Average patient age was 57 years (range, 36 to 80 years). Twelve patients (38 percent) were on chronic dialysis (end-stage renal disease), 18 patients (56 percent) had chronic renal insufficiency, and three patients (9 percent) had the diagnosis of acute renal failure at the time of surgery. Three patients in the chronic renal insufficiency group had a functioning renal transplant. Average follow-up was 16 months. Immediate postoperative complications occurred in 14 patients (42 percent of the 33 flaps). Overall perioperative mortality was 3 percent. Within the first 30 days there were two cases (6 percent) of primary flap failure; an additional four legs were lost as the result of complications related to their bypass grafts. There were no primary flap failures after 30 days; however, within the first year after surgery an additional seven limbs were lost as the result of progressive ischemia or infection, and an additional three patients died. This resulted in a 52 percent incidence of major morbidity or mortality during the first year and a 55 percent reconstructive success rate in survivors at 1 year. No significant difference was seen in postoperative morbidity or mortality when comparing the end-stage renal disease group to the chronic renal insufficiency group; however, patients with renal disease and diabetes tended to have poorer outcomes. Renal disease, especially renal disease associated with diabetes and peripheral vascular disease, can be a strong indicator of possible reconstructive failure. The surgeon and patient should be aware of the medical and surgical complications associated with this procedure at the outset.     

重症急性肾损伤患者经连续性肾脏替代治疗后肾功能恢复的影响因素

目的：通过研究重症急性肾损伤患者经连续性’肾脏替代治疗后肾功能恢复的影响因素,为重症急性肾损伤患者的诊治及预后提供科学依据。方法：选取2009年7月至2013年10月本院住院且采用CRRT治疗的284例重症急性肾损伤患者,记录患者的一般资料、APACHEII评分、血液生化指标、伴随症状及肾功能预后情况,将预后情况和各影响因素进行Logistic回归分析得出影响。肾功能恢复的影响因素。结果：284例重症急性肾损伤患者中,肾功能恢复有89例（31．33％）;肾功能恢复组的年龄、衰竭器官数、APACHEⅡ评分、动脉血二氧化碳分压、合并慢性肾脏病率及合并严重基础疾病率均低于肾功能未恢复组,而平均动脉压和血小板计数高于肾功能未恢复组（P〈0．05）,两组间合并机械通气率和合并少／无尿率无统计学差异（P〉0．05）;衰竭器官数、APAC—HEⅡ评分、合并严重基础疾病及AKl分期为CRRT治疗重症急性肾损伤患者肾功能恢复的危险因素。结论：CRRT治疗重症急性肾损伤的主要危险因素为衰竭器官数、APACHEⅡ评分、合并严重基础疾病及AKl分期。在临床治疗中,应正确评估病情,早期及时采取CRRT治疗,以提高生存率,促进肾脏功能恢复。     

Protein microarrays discover angiotensinogen and PRKRIP1 as novel targets for autoantibodies in chronic renal disease

Biomarkers for early detection of chronic kidney disease are needed, as millions of patients suffer from chronic diseases predisposing them to kidney failure. Protein microarrays may also hold utility in the discovery of auto-antibodies in other conditions not commonly considered auto-immune diseases. We hypothesized that proteins are released as a consequence of damage at a cellular level during end-organ damage from renal injury, not otherwise recognized as self-antigens, and an adaptive humoral immune response to these proteins might be detected in the blood, as a noninvasive tracker of this injury. The resultant antibodies (Ab) detected in the blood would serve as effective biomarkers for occult renal injury, enabling earlier clinical detection of chronic kidney disease than currently possible, because of the redundancy of the serum creatinine as a biomarker for early kidney injury. To screen for novel autoantibodies in chronic kidney disease, 24 protein microarrays were used to compare serum Ab from patients with chronic kidney disease against matched controls. From a panel of 38 antigens with increased Ab binding, four were validated in 71 individuals, with (n=50) and without (n=21) renal insufficiency. Significant elevations in the titer of novel auto-Ab were noted against angiotensinogen and PRKRIP1 in renal insufficiency. Current validation is underway to evaluate if these auto-Ab can provide means to follow the evolution of chronic kidney disease in patients with early stages of renal insufficiency, and if these rising titers of these auto-Ab correlate with the rate of progression of chronic kidney disease.     

A cervical ligamentum flavum cyst in an 82-year-old woman presenting with spinal cord compression: a case report and review of the literature

Introduction

Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease.

Case presentation

A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. Legionella pneumophila serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically.

Conclusions

This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.     

Should patients with renal failure associated with myeloma be dialysed?

In a study of renal function in multiple myeloma seven patients presented with renal failure and three developed it 16-106 months after diagnosis. All were dialysed. Infection with dehydration was a precipitating factor in all seven cases of acute or acute on chronic renal failure. Of these, two patients recovered normal renal function and one other was left with permanent renal impairment but no longer required dialysis. Results from the seven patients with acute renal failure and for the three with more chronic features support the practice of dialysis for all patients who present with renal failure. Dialysis is not indicated for those patients with progressive myelomatous disease. The study showed no evidence that chemotherapy permitted recovery from established renal failure. The prognosis in this elderly group is heavily dependent on the presence of cardiovascular or other degenerative disease.     

蝮蛇咬伤10885例救治分析

目的：探讨提高蝮蛇咬伤的救治水平。方法,回性总结我院１９７２－１９９９年蝮蛇咬伤患者１０８８５年,采用抗蝮蛇毒血清结合中药蛇伤合剂治疗;对合并急性呼吸衰竭的８５例患者,早期气管切开保持气管畅通,同时正压人工呼吸;对合并急性肾功能衰竭的１０３例患者,早期碱化尿液,应用足量利尿剂,必须时进行腹膜透析;对合并急性心功能衰竭的４３例患者,在应用强心、利尿、扩血管药物的同时,早期静脉给予山莨菪碱（６５４－２     

Peritoneal Dialysis in Chronic Renal Failure

The long-term results of intermittent peritoneal dialysis in long-term treatment of renal disease have yet to equal those of intermittent hemodialysis. However, further exploration and refinement of this technique is justified.Performed in acute stages of disease, both peritoneal dialysis and hemodialysis relieve the symptoms of uremia and specifically “buy time” for the patient so that proper medical or surgical therapy may be instituted. In acute situations, peritoneal dialysis is the procedure of choice, and is an important adjunct to more conventional treatment for chronic renal disease. It may be useful sometimes even in chronically hemodialyzed patients—for example, when the hemodialysis cannula for one reason or another is inaccessible because of clots, replacement, or infection. It is especially valuable when the hemorrhagic complications of uremia contraindicate hemodialysis treatment.Its use in chronic uremia remains sharply limited in time, but for brief periods chronic peritoneal dialysis appears to be a reasonably satisfactory means of prolonging life while awaiting homotransplant or decision for maintenance hemodialysis therapy.     

Pharmacokinetics of Drugs in Cachectic Patients: A Systematic Review

Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients.     

Replacement of renal function in uremic animals with a tissue-engineered kidney.

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.     

脂代谢异常对肾病的影响

肾脏疾病发展为慢性肾衰竭是个不可逆的过程,脂质代谢的异常,对肾病患者具有重要的影响。多项实验已经证实,即使在肾病的早期阶段,也会出现不同程度的脂质及脂类代谢的异常,高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、脂联素、瘦素等脂类代谢相关物质发生改变,不仅对血浆脂代谢产生影响,对于肾小球及肾小管的结构及功能也会有一定的损伤作用。肾病患者,如肾病综合征、慢性肾衰竭等疾病,多数有肾小球及肾小管间质的损伤,肾脏的脂毒性加重肾单位的破坏。随着人们对于慢性肾脏病认识的逐渐深入,降脂治疗的普遍应用,人们普遍认为改善血浆中脂类的水平,对于肾病的治疗,尤其对于慢性肾衰竭的预防具有重要作用。     

Renal stem cell reprogramming: Prospects in regenerative medicine

Stem cell therapy is a promising future enterprise for renal replacement in patients with acute and chronic kidney disease, conditions which affect millions worldwide and currently require patients to undergo lifelong medical treatments through dialysis and/or organ transplant. Reprogramming differentiated renal cells harvested from the patient back into a pluripotent state would decrease the risk of tissue rejection and provide a virtually unlimited supply of cells for regenerative medicine treatments, making it an exciting area of current research in nephrology. Among the major hurdles that need to be overcome before stem cell therapy for the kidney can be applied in a clinical setting are ensuring the fidelity and relative safety of the reprogrammed cells, as well as achieving feasible efficiency in the reprogramming processes that are utilized. Further, improved knowledge about the genetic control of renal lineage development is vital to identifying predictable and efficient reprogramming approaches, such as the expression of key modulators or the regulation of geneactivity through small molecule mimetics. Here, we discuss several recent advances in induced pluripotent stem cell technologies. We also explore strategies that have been successful in renal progenitor generation, and explore what these methods might mean for the development of cell-based regenerative therapies for kidney disease.     

Adult Polycystic Kidney Disease in a Rhesus Monkey (Macaca mulatta)

Adult polycystic kidney disease was diagnosed at necropsy in a 16-year-old rhesus monkey dead from renal failure. Both kidneys were enlarged and contained multiple cysts ranging from 0.1 to 4.0 cm in diameter. The age of onset of the clinical signs, terminal uremia, and the gross and histologic findings in this macaque were consistent with adult (type III) polycystic kidney disease of man.     

Bone morphogenetic proteins in development and homeostasis of kidney

Bone morphogenetic proteins play a key role in kidney development and postnatal function. The kidney has been identified as a major site of bone morphogenetic protein (BMP)-7 synthesis during embryonic and postnatal development, which mediates differentiation and maintenance of metanephric mesenchyme. Targeted disruption of BMP-7 gene expression in mice resulted in dysgenic kidneys with hydroureters, causing uremia within 24h after birth. Several experimental animal models of acute and chronic renal injury have all unequivocally shown beneficial effect of BMP-7 in ameliorating the severity of damage by preventing inflammation and fibrosis. Apart from the beneficial effect on kidney disease itself, BMP-7 improves important complications of chronic renal impairment such as renal osteodystrophy and vascular calcification.     

Hemodialysis removes uremic toxins that alter the biological actions of endothelial cells

Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure.     

Chronic Renal Disease—Some Sociological Aspects of Dialysis and Transplantation

Each year in California more than two thousand persons die of renal disease. Chronic uremia formerly was considered to have a hopeless prognosis. Recently the development of two procedures, chronic maintenance hemodialysis and renal homotransplantation, has offered substantial hope for the salvage of patients who otherwise would die of uremia.     

慢性肾衰竭患者治疗前后血清CysC,Hcy及PTH水平变化及临床意义

目的:探讨慢性肾衰竭(CRF)患者治疗前后血清胱抑素C(Cys C)、同型半胱氨酸(Hcy)及甲状旁腺激素(PTH)水平变化及临床意义。方法:筛选2013年12月至2014年12月我院就诊的CRF患者258例作为研究组,并选取同时期健康体检者258例为对照组,研究组患者入院后针对病情给予相应治疗,检测研究组治疗前后血清肌酐(Scr)、尿素氮(BUN)、Cys C、Hcy及PTH水平变化,分析不同分期CRF患者各指标的水平差异,并与对照组进行对比分析,分析Scr、BUN与Cys C、Hcy及PTH的相关性。结果:研究组血清Scr、BUN、PTH、Cys C和Hcy水平均明显高于对照组,异有统计学意义(P0.05),经过治疗后以上各项指标水平较前明显下降,差异有统计学意义(P0.05),但仍明显高于对照组,差异有统计学意义(P0.05);研究组患者Scr、BUN、Cys C、Hcy及PTH水平随着CRF分期发展而上升,其中尿毒症期肾功能衰竭期肾功能失代偿期肾功能代偿期,组间比较差异均有统计学意义(P0.05);采用Pearson相关性分析,研究组患者的Scr、BUN水平分别与Cys C、Hcy及PTH的水平呈正相关(r=0.731、0.642、0.813,P0.05;r=0.682、0.752、0.833,P0.05)。结论:Cys C、Hcy、PTH水平能够反映CRF患者临床治疗效果,反映疾病的严重程度,为CRF患者的诊断和预后提供参考,具有重要的临床意义。