Older candidates for kidney transplantation: Who to refer and what to expect?

The number of older end-stage renal disease patients being referred for kidney transplantation continues to increase. This rise is occurring alongside the continually increasing prevalence of older end-stage renal disease patients. Although older kidney transplant recipients have decreased patient and graft survival compared to younger patients, transplantation in this patient population is pursued due to the survival advantage that it confers over remaining on the deceased donor waiting list. The upper limit of age and the extent of comorbidity and frailty at which transplantation ceases to be advantageous is not known. Transplant physicians are therefore faced with the challenge of determining who among older patients are appropriate candidates for kidney transplantation. This is usually achieved by means of an organ systems-based medical evaluation with particular focus given to cardiovascular health. More recently, global measures of health such as functional status and frailty are increasingly being recognized as potential tools in risk stratifying kidney transplant candidates. For those candidates who are deemed eligible, living donor transplantation should be pursued. This may mean accepting a kidney from an older living donor. In the absence of any living donor, the choice to accept lesser quality kidneys should be made while taking into account the organ shortage and expected waiting times on the deceased donor list. Appropriate counseling of patients should be a cornerstone in the evaluation process and includes a discussion regarding expected outcomes, expected waiting times in the setting of the new Kidney Allocation System, benefits of living donor transplantation and the acceptance of lesser quality kidneys.     

Is it time to give up with calcineurin inhibitors in kidney transplantation?

Calcineurin inhibitors (CNIs) represent today a cornerstone for the maintenance immunosuppressive treatment in solid organ transplantation. Nevertheless, several attempts have been made either to minimize their dosage or to avoid CNIs at all because these drugs have the severe side effect of chronic nephrotoxicity. This issue represents a frontier for renal transplantation. The principal problem is to understanding whether the poor outcome over the long-term may be ascribed to CNIs nephrotoxicity or to the inability of these drugs to control the acute and chronic rejection B cells mediated. The authors analyze extensively all the international trials attempting to withdraw, minimize or avoid the use of CNIs. Few trials undertaken in low risk patients with an early conversion from CNIs to proliferation signal inhibitors were successful, but the vast majority of trials failed to improve CNIs side effects. To date the use of a new drug, a co-stimulation blocker, seems promising in avoiding CNIs with similar efficacy, better glomerular filtration rate and an improved metabolic profile. Moreover the use of this drug is not associated with the development of donor-specific anti-human leukocyte antigen antibodies. This point has a particular relevance, because the failure of CNIs to realize good outcomes in renal transplantation has recently ascribed to their inability to control the acute and chronic rejections B-cell mediated. This paper analyzes all the recent studies that have been done on this issue that represents the real frontier that should be overcome to realize better results over the long-term after transplantation.     

Robot-assisted kidney transplantation: Is it getting ready for prime time?

Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease, providing a better survival rate and quality of life compared to dialysis. Despite the progress in the medical management of KT patients, from a purely surgical standpoint, KT has resisted innovations during the last 50 years. Recently, robot-assisted KT (RAKT) has been proposed as an alternative approach to open surgery, especially due to its potential benefits for fragile and immunocompromised recipients. It was not until 2014 that the role of RAKT has found value thanks to the pioneering Vattikuti Urology Institute-Medanta collaboration that conceptualized and developed a new surgical technique for RAKT following the Idea, Development, Exploration, Assessment, Long-term follow-up recommendations for introducing surgical innovations into real-life practice. During the last years, mirroring the Vattikuti-Medanta technique, several centers developed RAKT program worldwide, providing strong evidence about the safety and the feasibility of this procedure. However, the majority of RAKT are still performed in the living donor setting, as an “eligible” procedure, while only a few centers have realized KT through a robotic approach in the challenging scenario of cadaver donation. In addition, despite the spread of minimally-invasive (predominantly robotic) surgery worldwide, many KTs are still performed in an open fashion. Regardless of the type of incision employed by surgeons, open KT may lead to non-negligible risks of wound complications, especially among obese patients. Particularly, the assessment for KT should consider not only the added surgical technical challenges but also the higher risk of postoperative complications. In this context, robotic surgery could offer several benefits, including providing a better exposure of the surgical field and better instrument maneuverability, as well as the possibility to integrate other technological nuances, such as the use of intraoperative fluorescence vascular imaging with indocyanine green to assess the ureteral vascularization before the uretero-vesical anastomosis. Therefore, our review aims to report the more significant experiences regarding RAKT, focusing on the results and future perspectives.     

Dynamics of circulating microparticles in chronic kidney disease and transplantation:Is it really reliable marker?

The deterioration of endothelial structure plays a very important role in the development of vascular diseases. It is believed that endothelial dysfunction starts in the early stage of kidney disease and is a risk factor of an unfavorable cardiovascular prognosis. Because a direct assessment of biological states in endothelial cells is not applicable, the measurement of endothelial microparticles(EMPs) detached from endothelium during activation or apoptosis is thought to be a marker of early vascular disease and endothelial dysfunction in children with chronic kidney disease(CKD). Few studies have shown increased circulating EMPs and its relationship with cardiovascular risk factors in patients with CKD.MPs contain membrane proteins and cytosolic material derived from the cell from which they originate. EMPs having CD144, CD 146, CD31+/CD41-, CD51 and CD105 may be used to evaluate the vascular endothelial cell damage and determine asymptomatic patients who might be at higher risk of developing cardiovascular disease in CKD and renal transplant.     

Choice of dialysis modality prior to kidney transplantation: Does it matter?

The population of patients with end stage renal disease (ESRD) is increasing, lengthening waiting lists for kidney transplantation. Majority of the patients are not able to receive a kidney transplant in timely manner even though it is well established that patient survival and quality of life after kidney transplantation is far better when compared to being on dialysis. A large number of patients who desire a kidney transplant ultimately end up needing some form of dialysis therapy. Most of incident ESRD patients choose hemodialysis (HD) over peritoneal dialysis (PD) as the modality of choice in the United States, even though studies have favored PD as a better choice of pre-transplant dialysis modality than HD. PD is largely underutilized in the United States due to variety of reasons. As a part of the decision making process, patients are often educated how the choice regarding modality of dialysis would fit into their life but it is not clear and not usually discussed, how it can affect eventual kidney transplantation in the future. In this article we would like to discuss ESRD demographics and outcomes, modality of dialysis and kidney transplant related events. We have summarized the data comparing PD and HD as the modality of dialysis and its impact on allograft and recipient outcomes after kidney transplantation.     

Renin-angiotensin system in the kidney: What is new?

The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin II(Ang II) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang IIformation or even active Ang II-derived peptides have now been described acting on Ang II AT₁ or AT₂ receptors, or in receptors which have recently been cloned, such as Mas and AT₄. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang II formation. This in situ formation, especially in the kidney, increases Ang II levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang II effects, improves the development of new drugs for treating hypertension and cardiovascular diseases.     

CE marking - what does it really mean?

Compliance with the Medical Devices Directive (93/42/EEC) became compulsory for all medical devices placed on the European market in June 1998. Under the directive, manufacturers are required to fulfil a number of requirements leading to the placing of the CE mark on their devices. However, many questions still remain. Not all manufacturers are aware of their responsibilities and not all purchasers are aware of the true meaning of the CE mark. It is vital to understand the purpose of the regulations, the definition of 'medical device', the importance of complying with the manufacturer's intended purpose and instructions, the role of quality systems and clinical investigations in the compliance process, and the decisions which may be made by the manufacturers. It is also important to realise that whilst the directive, if correctly applied and enforced, brings benefits to the medical industry and patients, it is not a substitute for professional judgement in the purchasing process.     

Squamous cell carcinoma in situ in skin: what does it mean?

Squamous cell carcinoma in situ (SCCIS) is a frequently reported diagnosis by pathologists. The dermatologists bases their management of the patient on this diagnosis. However, SCCIS can be seen in a variety of clinical situations. The pathologic diagnosis of SCCIS must be correlated with clinical data to arrive at a correct diagnosis and therefore appropriate management of the patient.     

Systemic steroids in the treatment of psoriasis: what is fact,what is fiction?

Background The use of systemic steroids in the treatment of psoriasis is not recommended by dermatological textbooks and guidelines because of the risk of disease deterioration after dose reduction or withdrawal. In contrast to these recommendations, a recent analysis using data from a German nationwide healthcare insurance revealed that systemic steroids were the most frequently prescribed drugs for psoriasis by general practitioners, internal medicine physicians and dermatologists. Objective As there is an obvious discrepancy between the use of systemic steroids for psoriasis and the reported adverse effects, a non‐systematic literature search starting 1950 until today was performed to address beneficial and adverse effect of systemic steroids in psoriasis. Methods Non‐systematic literature search. Results Regarding the widespread use of systemic steroids in psoriasis and other medical conditions taking the high prevalence of psoriasis of 2–3% at least in Caucasians into consideration, there is a remarkable lack of literature addressing adverse effects such as rebound, pustular or erythrodermic flares or even new occurrence of psoriasis in patients with a negative disease history. Conclusion A re‐evaluation of the treatment of psoriasis and/or psoriatic arthritis with systemic steroids is necessary.     

Lowering vascular calcification burden in chronic kidney disease: Is it possible?

High prevalence of atherosclerosis and arterial calcification in chronic kidney disease is far beyond the explanation by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcification. Strategies to lower vascular calcification burden in chronic kidney disease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate binders, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on efficacy and patient outcomes are necessary. Several large randomized controlled trials have confirmed the lack of benefit of statin in attenuating the progression of vascular calcification.     

Is serum copeptin a modifiable biomarker in autosomal dominant polycystic kidney disease?

The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]. However, serum copeptin is strongly correlated with creatinine, and its additional value as a prognostic biomarker over estimated glomerular filtration rate and TKV is not certain. It has also been suggested that copeptin could be a predictive biomarker to select ADPKD patients who are most likely to benefit from AVP-modifying therapies, but prospective data to validate this assumption are required. In this regard, long-term randomised clinical trials evaluating the effect of prescribed water intake on renal cyst growth may contribute to addressing this hypothesis. In conclusion, although serum copeptin is aligned with the basic pathogenesis of ADPKD, further rigorous studies are needed to define if it will contribute to enabling the delivery of personalised care in ADPKD.     

More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients

Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history. The unique aggressiveness of SCCs in KTRs increases patient morbidity, due to the high rate of new lesions requiring treatment, frequently surgical excision. Oral nicotinamide shows promise in the chemoprevention of the especially aggressive non-melanoma skin cancers which occur in KTRs. This benefit might be conferred via its inhibition of sirtuin enzymatic pathways. Nicotinamide’s concurrent hypophosphatemic effect may also partially ameliorate the disturbed calcium-phosphorus homeostasis in these patients-a putative risk factor for mortality, and graft failure. Conceivably, a phase 3 trial of nicotinamide for the prevention of non-melanoma skin cancers in KTRs, lasting at least 12-mo, could also incorporate imaging and laboratory measures which assess nicotinamide’s impact on subclinical cardiovascular and chronic kidney disease risk, and progression.     

Psoriasis: what is new in nonbiologic systemic therapy in the era of biologics?

Psoriasis is a common debilitating disease significantly affecting the quality of life of the patients. Majority of the psoriasis patients have mild disease which can be managed by topical therapies. Around 30% of the psoriasis patients require systemic therapy during the course of their disease. There is a vast array of drugs for the treatment. Methotrexate, cyclosporine and retinoids are the most commonly used conventional systemic drugs. Newer studies provide insight into their more effective and safer use and as combination therapy with biologics. In recent times, many new drugs with novel mechanisms of action other than biologics have been tried in psoriasis. In this article, we have reviewed the current developments and new found role of the conventional drugs as well as the newer nonbiologic systemic drugs in the treatment of psoriasis.