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Challenges and Opportunities in Acute Kidney Injury

Challenges and Opportunities in Acute Kidney Injury

Geoff Burnhill, MBBS, MChem, PgDip, Ella Davidson, Benedict Griffiths, MBBS BSc (Hons), and Jon Lillie, MBBS BSc

Abstract

Background: Children admitted to intensive care with diabetic ketoacidosis are at risk of acute kidney injury. Recent UK guidelines recommends against restricted fluid provision due to a theoretical risk of kidney injury. To date no data has been published that documents this risk in an intensive care cohort.

Aims: To describe the natural history of acute kidney injury in patients admitted with diabetic ketoacidosis in whom a restrictive fluid regime was provided.

Methods: Retrospective analysis, within a UK Pediatric Intensive Care Unit. Between January 2011 and December 2020 219 patients were referred to the South Thames Retrieval Service with Diabetic Ketoacidosis, of whom 52 were admitted to Evelina PIC. 49 of these records were complete and used for analysis of acute kidney injury stage using Kidney Disease: Improving Global Outcomes criteria measured by serial creatinine. Clinical outcome at discharge from Pediatric Intensive Care was also recorded.

Results: 19 out of 49 (38%) patients had acute kidney injury (17 present on admission to pediatric intensive care). Three patients required renal replacement therapy though all of them went on to re-establish their baseline renal function. This compares favourably to published data documenting an acute kidney injury incidence of 43-64% in general paediatric and pediatric intensive care cohorts.

Conclusion: In the context of diabetic ketoacidosis, use of a restrictive fluid regime was not associated with higher levels of acute kidney injury than other studies and renal function recovery was observed in all patients followed up.

Kauther I. Layas, Prabal K. Chatterjee, and Ananth S. Pannala

Abstract

Acute kidney injury is characterized by abrupt failure of kidney function, sometimes leading to chronic kidney disease, and is associated with significant morbidity and mortality. However, there is no clear effective therapeutic solution and treatment is mainly based on either alleviation or removal of the possible cause and/or renal replacement therapy. Oxidative stress has been indicated as one of the main pathophysiological pathways in the development of acute kidney injury. Various treatments including antioxidants, inflammatory mediators and genetic modifiers have been proposed to for the treatment of this condition. Epidemiological studies show lower incidence of kidney failure with higher consumption of antioxidants. However, the data is inconclusive due to their physicochemical properties, bioavailability or toxicity. Novel drug delivery systems such as liposomes and nanoparticles have been proposed to overcome the pharmacodynamic and pharmacokinetic barriers. This review provides a brief introduction to acute kidney injury and the different factors involved in its pathology, focusing on oxidative stress. It also covers details of antioxidant use as preventive and/or treatment option. It will summarise their limitations as free drugs and the possible improvement in their bioavailability by two main novel drug delivery systems: liposomes and polymeric nanoparticles. Other therapies such as inflammatory mediators and genetic modifiers are also discussed briefly.

Kyle Dickinson, Chantal Bernard, Diana Iglesias, and Paul Goodyer

Abstract

The emergence of nephron progenitor cells (NPCs) in early embryonic life leads to the many rounds of nephrogenesis that result in a richly endowed kidney by the end of gestation. A delicate balance between NPC differentiation and self-renewal must be maintained to guarantee optimal nephron endowment. Genetic errors which disturb NPC cell fate can result in premature NPC depletion and renal hypoplasia/dysplasia or permit the β-catenin mutations that accompany malignant transformation into a Wilms tumor. Retention of a small population of NPCs scattered throughout the adult kidney are important for recovery from acute tubular injury later in life. In this review, we track the origin and characteristics of NPC, describe the phase of NPC priming prior to nephron induction and describe NPC differentiation during nephrogenesis. We then cover the role of NPC in human renal disease, including mechanisms by which quiescent NPCs repair the injured adult kidney and the human diseases linked to dysfunction of NPCs.

Risk of Acute Kidney Injury Following Mytomicin C Resorption during Hyperthermic Intraperitoneal Chemotherapy

Piet de Witte, Peter Bruins, Djamila Boerma, and Veronique Kemmel

Abstract

Background:     Surgical cytoreduction and simultaneous hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is a common treatment for peritoneal carcinomatosis. During intraperitoneal chemotherapy, mitomycin C is frequently used. Mitomycin C is known to be nephrotoxic. Little is known about the effect of systemically absorbed mitomycin C on renal function during HIPEC surgery.

Methods: In twenty-two patients undergoing cytoreductive surgery and HIPEC for peritoneal carcinomatosis the systemic levels of mitomycin C were measured in plasma. The relation of plasma levels of mitomycin C with duration of surgery and complexity of surgery was evaluated.

Furthermore, we evaluated the relationship between systemic mitomycin C levels and renal function.

Results Two patients out of a total of 22 patients developed acute kidney injury. In these patients, preoperative creatinine level increased from (1) 109 μmol/L to maximum 890 μmol/L on the 6th postoperative day after which renal replacement therapy was started and (2) from 67 μmol/L to 213 μmol/L. Whereas maximum plasma levels of mitomycin C in these 2 patients were 145 μg/L and 280 μg/L compared to the levels in the other patients (167 μg/L ±80.8). Peak levels of plasma creatinine were on post operative day 2. None of the other patients needed renal replacement therapy. Eight patients showed significant increase of plasma creatinine levels, i.e. >20% increase from preoperative values. We did not observe a correlation between complexity of surgery, increased absorption of mitomycin C, higher mitomycin C plasma levels and signs of kidney injury.

Conclusions:     Systemic absorption of mitomycin C during HIPEC surgery is independent to extension of cytoreductive surgery and duration of surgery. In this small study group, we observed an impairment of renal function which may be related to systemic absorption of mitomycin C. Further research is warranted to answer possible association of mitomycin C levels in patients at risk for development of AKI.

Dhanya Mohan, Amna Khalifa Alhadari, Dileep Kumar, Sima Abdolla Nejad, Rahaf Mohamad Wardeh, Batool Khan, Madheeha Mahmood, Zuha Fathima, and Mohammed Railey

Abstract

Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy, and, in rare cases renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.

Prathap Kumar, Blessvin Jino, and Manu Rajendran

Abstract

Iodinated contrast media are required in all cases who undergo coronary angiography and percutaneous coronary interventions (PCI). Though the modern contrast media (both low-osmolar and iso-osmolar) have lesser adverse effects than the older generation contrast media, they may lead to life threatening complications in few cases. Contrast induced acute kidney injury (CI-AKI) is one such complication where the presentation may vary from asymptomatic mild elevation in serum creatinine to life threatening uremia. Various pre-procedural and procedural steps are followed commonly to prevent CI-AKI and reducing the contrast volume is one of the most important steps. Indeed, multiple studies have proven that reducing the contrast volume during PCI reduces the risk of CI-AKI. More recently, intra-coronary imaging guided zero-contrast PCI has emerged as an important method to prevent CI-AKI. Though randomised controlled trials comparing low-contrast PCI and zero-contrast PCI are lacking, this technique is being used widely by experienced operators. Technical expertise in complex PCI and meticulous analysis of intra-coronary imaging, particularly intravascular ultrasound (IVUS), are mandatory for this procedure.

Ioannis Koulouridis and Efstathios Koulouridis

Abstract

Cis-diamino-dichloro platinum is one of the most widely used antineoplastic drugs. It is used therapeutically in 10-20% of all cancers. It is active against a variety of solid tumors such as head, neck, lungs, ovaries, cervix, bladder, etc. The therapeutic use of the drug is combined with significant toxicities such as: neurotoxicity (85-95%), ototoxicity (23-50%), nephrotoxicity (30%), gastrotoxicity and bone marrow suppression.

Nephrotoxicity is a limiting condition since repeated episodes of acute kidney injury may lead to chronic kidney disease which then develops regardless of drug discontinuation. Unfortunately, nephrotoxicity and antineoplastic activity share common molecular mechanisms at the cellular level. Therefore, any attempt to reduce nephrotoxicity implies a reduction in the antineoplastic effect.

Continuing investigation of the mechanisms underlying cisplatin nephrotoxicity upon molecular level has provided an enormous amount of knowledge concerning accumulation of the drug in renal epithelial cells, cellular damage via destruction of cellular organelles and cellular proteins as well as induction of repair and rescue mechanisms such as autophagy toward the improvement of cell survival. All these metabolic pathways are currently candidates for therapeutic intervention. Moreover, new therapeutic approaches based upon natural derivatives such as phytochemicals are under laboratory investigation hopping to add more effective treatments in cisplatin nephrotoxicity.  

In the present review we analyze the mechanisms of drug-induced cellular damage, the evidence so far, and developments in the effort to reduce nephrotoxicity without loss of drug activity.

Ashish Vasudev, BSc (Hons), MBChB, Abdus Samee Wasim, BSc (Hons), MBBS, MRSC, Akash Sharma, FRCS(Tr&Orth), Yuvraj Agrawal, FRCS(Tr&Orth)

Abstract

Hip and knee arthroplasty is an extremely successful and cost-effective procedure that is widely performed to restore function and alleviate pain. The arrival of the SARS-CoV-2 virus (COVID-19) brought significant disruptions to delivery of surgery worldwide, including lower limb arthroplasty. Three years on from the start of the pandemic the effects of the virus are still present. This literature review aims to explore current data published from our single specialty orthopaedic centre and data collected nationally and internationally, on the impact of the COVID-19 pandemic on lower limb arthroplasty.

Elective hip and knee arthroplasty in the UK fell by approximately 40% and 50% respectively (2020 vs 2019) and by the end of 2021 the number of procedures completed still remained below pre-pandemic levels. As a result, elective waiting times are longer than ever before, with more patients suffering worse health states and a significant impact on quality of life. The UK National Hip Fracture Database showed an active COVID-19 infection was associated with a three-fold greater risk of 30-day mortality post lower limb arthroplasty. Several reports have also correlated peri-operative COVID-19 infection with increased risk of systemic complications with the virus such as pneumonia, deep vein thrombosis, pulmonary embolisms, acute kidney injury and myocardial infarction to name a few.

NHS England provided guidelines for safe recommencement for elective operating. Upon adoption of these recommendations, several orthopaedic units found similar rates of post-operative complications and mortality to pre-pandemic levels, demonstrating that safe elective care can be delivered even during an emergency pandemic setting. The development of rapid testing, use of personal protective equipment and introduction of pre- and post-operative isolation protocols were effective measures to allow elective surgery to restart. For infected individuals awaiting surgery, delays of at least seven weeks are recommended to reduce complication rates. There is limited literature discussing the impact of the vaccine on post-operative complications and mortality. Early reports however have suggested vaccinated individuals benefit from a reduced mortality risk in emergency cases of hip fracture surgery, but this is an area which would benefit from further research.