Renal tubular handling of drugs

The renal excretion of drugs is a vectorial quantity, the resultant of physiologic mechanisms that have directional orientation and magnitude. Magnitude is limited by a variety of extrarenal factors including plasma protein binding and the volume of the total body water. The contributions of the glomeruli and tubules to excretion varies with age. This fact has clinical relevance, especially in newborn children and older patients. Although protein binding reduces the amount of a drug that can be filtered, it usually does not alter the rate of proximal tubular secretion of charged organic molecules. Reabsorption of the filtered fluid from tubular lumens creates concentration gradients favoring the reabsorption of drugs, but the movement of drug molecules out of luminal fluid is hindered by the formation of polar drug metabolites in the liver. Although there are only a few examples in the literature, it is probable that many drugs are reabsorbed by a carrier-mediated process located in the proximal tubules.     

Renal tubular acidosis following intestinal bypass: an etiological study

Nine cases of the distal type of renal tubular acidosis (RTA) following intestinal bypass were found. Diagnosis was based on inability to acidify the urine to pH values below 5.40 despite systemic acidosis. Acidosis, if not present, was induced by giving ammonium chloride 0.1 g/kg body weight. Patients were examined for diseases known to cause RTA but no already known etiological factor was found. Hyperoxaluria was found in eight of the nine cases with RTA, while not present in patients without RTA or in obese control patients. A causal relationship between hyperoxaluria and RTA is suggested though not proved. Cases reported in the literature of renal damage following bypass are summarized and discussed in relation to presence of hyperoxaluria and RTA.     

Polyomavirus-associated nephropathy: update on antiviral strategies

Polyomavirus-associated nephropathy (PVAN) is a major complication of kidney transplantation. Many centers respond to PVAN by reducing immunosuppression. Concern over precipitating rejection, as well as situations in which some PVAN-afflicted individuals have multi-organ transplants, can make reduction of immunosuppression undesirable. In these cases, effective antiviral strategies would be useful. This article describes clinical observations and experiences with 3 different antiviral protocols. Two protocols address antiviral treatment of nephropathy (cidofovir in one, and leflunomide in the other). The third protocol examines fluoroquinolone control of polyoma urinary excretion. Patients responded to all 3 strategies. These promising approaches deserve further evaluation with prospective controlled studies.     

Renal tubular acidosis

Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment of underlying disease, correction of electrolyte imbalance, particularly hypokalemia and hyperkalemia, and most importantly, the use of alkali. This will prevent or reduce all the various complications.     

肾小管酸中毒

由于肾脏酸化功能障碍所产生以高氯性代谢性酸中毒为主要表现的临床综合征群称为肾小管酸中毒 (ＲＴＡ) ,其共同特征是肾小管的泌氢或重吸收碳酸氢根障碍 ,使血中ＨＣＯ-3 下降 ,大多伴有钾、钙、磷等代谢紊乱。肾脏的酸化功能为重吸收由肾小球所滤过的相当部分ＨＣＯ-3 及再生大量的ＨＣＯ-3 ,后者用以补充体内缓冲液中由于缓冲大量来源于饮食及代谢过程中产生的酸性物质而被消耗的碱储 ,从而保证体内酸碱处于相对恒定状态。肾脏的排酸由三部分组成 :铵的排泌 ,可滴定酸的排泌以及ＨＣＯ-3 的重吸收。酸化功能主要由近端肾小管及远端肾单位…     

Renal transplantation update

Various factors affect the outcome of renal transplants in humans. Matching for HLA-A, -B, and -DR histocompatibility antigens improves survival rates for renal allografts from first cadaver donors. Zero-HLA-A- and -B-antigen-mismatched grafts and two-HLA-DR-antigen-matched grafts do better, although results differ depending on the recipient's primary renal disease. Pretransplant third-party blood transfusions significantly improve survival rates of cadaver donor allografts. The mechanism of this beneficial effect has not been identified; however, blood transfusions probably do not "select out" high responders among potential recipients by stimulating the production of lymphocytotoxic antibodies. Cyclosporine has been heralded as a potent, nonspecific immunosuppressive agent that will significantly improve renal allograft survival rates. The selectivity of cyclosporine's effect on T lymphocytes is advantageous; however, its side effects, especially nephrotoxicity, may limit its usefulness. Attention to the potential surgical complications of renal transplantation can significantly reduce morbidity and mortality.     

新型冠状病毒肺炎抗病毒药物与心律失常的关系

新型冠状病毒肺炎(COVID-19)于2019年12月,在中国武汉部分地区爆发以来,疫情来势凶猛,对人类健康构成严重威胁,其病原体为一种β属的新型冠状病毒(2019-nCoV)。针对冠状病毒的治疗目前暂缺乏特效药物,随着疾病认识的深入和诊疗经验的积累,国家卫健委已推出《新型冠状病毒肺炎诊疗方案》试行第六版指导疾病的诊治。目前所试用的抗病毒药物多基于体外试验的结果,尚未经过随机双盲对照试验的检验,其疗效需在临床应用中进一步评价。这些抗病毒药物的心律失常不良反应应予重视。     

Characteristics of antiviral drugs

This article summarizes the principal characteristics of the drugs used to treat viral infections, with the exception of human immunodeficiency virus infection. It includes antiviral agents active against herpes virus, cytomegalovirus, hepatitis B and C virus, and respiratory viruses, such as influenza and respiratory syncytial virus. Dosage according to the indication, dose adjustment in the case of renal or hepatic insufficiency, significant pharmacokinetic characteristics, and the main adverse effects and interactions are described.     

Renal tubular acidosis and autoimmune liver disease

Forty-two patients with autoimmune liver disease have been investigated. Renal tubular acidosis was detected in 60% of the patients with primary biliary cirrhosis, in 30% with active chronic hepatitis, and in one out of seven cases with cryptogenic cirrhosis. The presence of the defect of renal acidification was not related to the level of plasma potassium, copper, or total globulin, nor to the pattern of immunological abnormalities detected in the serum. It is suggested that autoimmune liver disease and renal tubular acidosis may be part of a systemic disorder in the pathogenesis of which immunological mechanisms are involved.     

Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features,pathophysiology and treatment

Objectives: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment.

Methods: A thorough PubMed search was performed using as main keywords: ‘paroxysmal nocturnal hemoglobinuria’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘eculizumab’.

Results: PNH’s etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease’s major clinical features, like intravascular hemolysis, cytopenias and thrombosis. PNH is often underdiagnosed, mainly due to its occasional mild manifestations and to its ability to mimic other severe clinical conditions. Various mechanisms have been proposed for the kidney damage attributed to the release of cell-free heme and free iron, including inflammatory response, oxidative stress, nitric oxide depletion, renal ischemia, membrane damage and apoptosis. Eculizumab, a terminal complement inhibitor, provides a safe and effective treatment option, especially when it is initiated early in the presence of kidney damage.

Discussion: Kidney injury is a poorly investigated clinical feature of PNH that affects a significant portion of patients. Increased awareness is needed by physicians to recognize the early signs and symptoms of acute and chronic renal insufficiency, so as to initiate the necessary therapy. It is also important to re-evaluation of PNH-specific treatments during the course of the disease.

Conclusion: Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.     

慢性乙型肝炎特殊患者抗病毒治疗专家共识:2015年更新

<正>抗病毒治疗是慢性乙型肝炎(CHB)治疗的关键。近年来随着抗病毒治疗不断进展,一般患者的治疗逐渐趋于规范,而CHB特殊患者由于循证医学证据相对不足、相关指南无统一的推荐意见等原因成为临床治疗的难点。为进一步规范这些特殊患者的治疗,2010年《中华实验和临床感染病杂志(电子版)》、《临床肝胆病杂志》与《中国肝脏病杂志(电子版)》编辑部组织相关专家对相关资料进行整理与分析,形成了《慢性乙     

Metformin: an update

Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.