Chronic Kidney Disease +/- Dialysis
Presentation and diagnosis
- Symptoms of CKD are non specific
- edema, hypertension, and/or decreased urine output
- More significant: weakness and easy fatigability, anorexia, vomiting, mental status changes, and seizures
- Disease specific - eg ANCA associated vasculitides, lupus, IgA nephropathy following an upper respiratory tract infection, TTP etc
- Ix include serology, imaging +/- biopsy, proteinuria, casts etc
- T2DM, hypertension, analgesic consumption, gout, vasculitides, idiopathic glomerulonephritis, amyloid, sarcoid, renal vascular disease
- anuria and symtoms of fluid overload
- uraemic complications - itch, encephalopathy, neuropathy, pericarditis, lethargy
- hypertension
- anaemia, usually multifactorial - Fe deficiency if having uraemic bleeding, haemolysis, EPO deficiency, BM supression, aluminium toxicity
- Bone disease - renal osteodystrophy, adynamic bone disease, osteoporosis, osteomalacia
- Metabolic complications - hyperkalaemia
- Cardiovascular complications
- Goals of therapy are to (1) confirm diagnosis (2) optimise symptoms (3) reduce progression (4) manage complications (5) Treat specific cause (6) Ensure appropriate follow-up
- Confirm diagnosis with the necessary investigations
- all patients should have kidney US, basic blood tests, urine casts, microscopy, active sediment, albumin creatinine ratio
- Optimise symptoms
- General non-pharmacological strategies
- Kidney Health Australia has a suite of brochures, health fact sheets, publications and self-management resources that give precise, up to date health promotion and disease prevention messages
- Lifestyle interventions for targeted cardiovascular risk - remembering that CKD is a coronary artery disease risk equivalent more significant than diabetes itself
- recommended that after GFR <30 one should see an accredited dietician
- Neuropathic pain - massages, hot-cold compresses, anti-neuropathic agents such as pregabalin
- muscle cramps - massages, stretching exercises, tonic water may help
- restless legs - massages, relaxation techniques, make sure Fe is replete, consider dopamine agonists
- anaemia - mentioned later
- uraemia - dialysis, or if palliative approach then symptomatic management
- General non-pharmacological strategies
- Reduce progression
- Treat specific cause eg lupus, ANCA vasculitis
- Manage hypertension - target <140/90 in CKD, 130/80 in diabetes. Non pharmacological lifestyle methods such as increased physical activity within the limits of the patient, aim to initiate ACE-inhibitor/ ARB first - review after 2 weeks, if not below target then check compliance and optimise adherence, add calcium channel blocker or beta-blocker or diuretic, review after 2 weeks
- Manage other cardiometabolic risk factors - consider statin if absolute cardiovascular risk >10% in 10 years, reduce smoking, aim for weight loss if overweight (4.4 mmHg for 5.1kg weight lost), adopt DASH diet (DASH diet: 5.5 mmHg for normotensives; 11.4 mmHg for hypertensives), Salt no more than 6g/d, increase physical activity to 30 mins mod intensity on almost every day of the week
- Manage complications
- Anaemia - target Hb 100 - 115, ferritin 200 - 500, transferrin sats 20 - 30%, EPO agents such as weekly aranesp, aim monthly increase of 10g/L, no quicker as get hypertension or seizures. EPOA can only be supplied by a nephrologist
- Patient may have EPO resistant anaemia, therefore consider other causes
- Acidosis - sodibic 840mg once daily to two tablets BD, titrate HCO3 > 22, care should be taken as it is a significant volume load
- Bone health - low turnover osteomalacia, osteitis fibrosa, adynamic bone disease. Driven by raised PO4 and low activated vitamin D. Targets are PO4 [0.8 - 1.6], Ca 2.1 - 2.4, [Ca x PO4 < 4]
- Control PO4 with dietary phosphate restriction and phosphate binders - calcium carbonate, sevelamer [for pt on dialysis], lanthanum [for pt on dialysis]
- Use calcitriol (D3) or paracalcitol to titrate up calcium
- Measure PTH 2-3 monthly
- PTHectomy for autonomous i.e. high PTH and calcium, whilst off all calcium and vitamin D agents
- Calcimimetics
- Parthyroid sensitised to respond to lower calcium levels
- No survival benefit but can decrease PTH, calcium and phosphate, [Ca x PO4}
- Immunise against influenza and pneumococcus
- Albuminuria - aim 50% decrease in ACr using ACE-inhibitors/ ARBS
- Screen for depression
- SSRIs (selective serotonin reuptake inhibitors) have established safety in people with CKD
- Volume overload
- may need more sessions of dialysis
- Need very large doses of loop diuretics
- Potassium
- Target K < 6
- Manage with low K diet, correct acidocis, avoid salt substitutes, cease potassium sparing diuretics
- Nutrition
- Target albumin > 35
- when GFR < 30 --> refer to dietician
- target 0.75-1g/kg protein
- Anaemia - target Hb 100 - 115, ferritin 200 - 500, transferrin sats 20 - 30%, EPO agents such as weekly aranesp, aim monthly increase of 10g/L, no quicker as get hypertension or seizures. EPOA can only be supplied by a nephrologist
- Consider when GFR <20, and offered if pt expected to live > 1 year
- Native AV fistula should always be attempted to be created, fistula's should be created distally in the upper limb if possible from the wrist (radiocephalic) working proximally (eg brachiocephalic). If a native graft cannot be fashioned, then a synthetic graft is preferred over a catheter.
- Patients using catheters, had higher risks for: all-cause mortality, risk ratio (RR) =1.53 (95%CI: 1.41-1.67, P<0.01); fatal infections RR = 2.12 (95%CI: 1.79-2.52, P = 0.82); and cardiovascular events RR = 1.38 (95%CI: 1.2-1.54, P=0.47) compared with individuals using fistulae.
- All patients, especially those with co-morbid conditions, should be referred to a vascular access surgeon well in advance of the anticipated need for haemodialysis.
- Primary determinants of mode of initial dialysis include the preference of a fully-informed patient, absence of medical and surgical contraindications, and resource availability
- When dialysis modality is not determined by preference of a fully-informed patient, absence of medical and surgical contraindications and resource availability, consider using continuous ambulatory peritoneal dialysis (CAPD) (not automated peritoneal dialysis [APD]) in preference to haemodialysis to better preserve residual renal function (RRF) and allow graded introduction of dialysis.
- Commence dialysis when GFR falls below approximately 10 mL/min/1.73 m2 if there is evidence of uraemia or its complications such as malnutrition.
- If there is no evidence of uraemia or its complications including malnutrition, commence dialysis when GFR falls below approximately 6 mL/min/1.73 m2
Renal +/- Pancreas Transplant
History
- Cause of CRF: eg T2DM, glomerulonephritis, reflux nephropathy, APKD
- Pre-transplant evaluation
- Tissue typing
- ABO compatibility. Incompatibility obviously affects graft survival
- Tissue typing (HLA A, B, DR)
- cardiorespiratory status: intermediate risk --> stress test (dobutamine ECHO, stress MIBI), high risk --> coronary angiogram, ABG, pulmonary function tests
- Nutritional status
- Infection/ malignancy status, screening for absolute contraindications
- active/ disseminated malignancy
- uncontrolled/ untreated infection
- chronic infection
- unacceptable anaesthetic risk
- Psychosocial:
- adherence/ compliance
- insight
- MH comorbidities
- Tissue typing
- Transplant Hx: Date, ABO match, HLA match, Living donor or decreased donor, CMV status of donor and recipient
- Combined Kidney/ pancreas transplant
- goals of transplantation --> restore glucose-regulated endogenous insulin secretion, arrest progression of diabetic complications, improve quality of life
- Usually done in conjuction with renal transplant - in this setting it can mean that the transplanted kidney will survive longer
- Could have pancreas only transplant if there is frequent, acute, severe metabolic complications (hypoglycemia, marked hyperglycemia, ketoacidosis), significant difficulty with insulin therapy, and consistent failure of insulin-based management to prevent acute complications
- islet cell Tx still evolving, only done in clinical trials setting
- high rate of insulin independence with pancreas Tx (graft survival 81, 55, and 51 percent at one, three, and five years)
- Unique immunosupressive requirements with pancreas Tx --> tacrolimus instead of cyclosporin, mycophenolate instead of azathioprine
- Episodes of rejection follow renal rejection
- Surgical Hx: Intra-operative complications, ICU length of stay, tolerability of induction regime
- Induction regime: Triple therapy + basiliximab (IL2 R antibody)
- Maintenance: Triple or dual therapy
- Complications:
- Rejection episodes
- hyper-acute rejection may have complicated a previous renal Tx. This is rare and untreatable. This is due to preformed antibodies, and is predictable by cross matching process
- This will lead to loss of graft
- Acute rejection: diagnosed on biopsy, heralded by increasing serum creatinine, decreased urine output. Classically T cell mediated, broad DDx include ATN, drugs, obstruction, pre-renal impairment. Pathology is broken down into cellular (tubulitis, interstitial infiltrate), vascular (endothelialitis, glomedulitis, haemorrhage), antibody (PMNs, C4d+ staining).
- Cellular rejection: Rx 250mg-1g methylprednisone x 3-5 days, usually reverses 90% of acute rejection episodes, if steroid resistant may need anti-T cell antibodies (ATG, OKT3), these reverse 75% of steroid resistant rejection episodes, if still refractory, then can give high dose tacrolimus and mycophenolate
- Antibody rejection: IVIG, Plasmapheresis
- Chronic rejection: common, occuring in 30% of transplant Pts, of immune and non-immune aetiology, presenting with progressive renal dysfunction, proteinuria and hypertension
- hyper-acute rejection may have complicated a previous renal Tx. This is rare and untreatable. This is due to preformed antibodies, and is predictable by cross matching process
- Infections in immunocompromised host
- Prophylaxis:
- Valganciclovir prophylaxis for CMV+ recipient or CMV + Donor --> CMV - recipient Careful about chance of CMV disease
- Bactrim prophylaxis for 6/12, if cannot tolerate this then nebulised pentamidine
- Fungal prophylaxis with fluconazole
- BK nephropathy: Occurs because BK virus reactivation occurs secondary to immunosupression, Found by decoy cells on urine cytology and BK virus PCR (urine/ blood), Rx by decreasing immunosupression
- Prophylaxis:
- Declining renal function:
- Broad differential, work through the causes and pre-test probability modified by timing post transplant. Differentiate into pre-renal, renal and post-renal causes
- Immediate (<48h) - need to consider surgical causes strongly, but rejection and CNI toxicity also occur
- Early (<4 weeks) - consider in addition to surgical causes haemolytic uraemic syndrome - look for evidence of a microangiopathic blood film (assoc with infection, CNI, mTOR toxicity, OKT3 use, acute vascular rejection, Rx with PLEX/ FFP).
- Late (>4 weeks): Consider all the above but also renal artery stenosis
- Re-occurence of disease
- Especially metabolic if not controlled and a number of glomerulonephritis
- Drug side-effects:
- Cyclosporin: MOA [binds to cyclophilins --> inhibits calcineurin which is a phosphatase --> number of transcription factors cannot translocate to nucleus --> reducing transcriptional activation of early cytokine genes for IL-2], therapeutic drug monitoring [troph, AUC, 2hr post dose], Toxicity [nephrotoxicity secondary to acute intra-renal vasospasm, chronic stripped fibrosis, TTP/ HUS, low Mg, neurotoxicity with tremor, Hirsutism, gingival hyperplasia ]
- Tacrolimus: MOA [binds to FK506 --> inhibits calcineurin which is a phosphatase --> number of transcription factors cannot translocate to nucleus --> reducing transcriptional activation of early cytokine genes for IL-2], Toxicity [less nephrotoxicity, more post Tx DM, no gingival hyperplasia, less hyperlipidaemia, less HTN compared with cyclosporin]
- Mycophenolate: MOA [Reversible inhibitor of inositol monophosphate dehydroganase (IMPDH) in purine biosynthesis --> lymphocytes can only synthesise purines through de-novo pathway and there is no salvage pathway + salvage pathway unaffected in other cells], largely replacing azathioprine with lower rates of rejection, toxicity [myelosuppression (more lymphopenia and anaemia, less thrombocytopenia), GIT (nausea and diarrhoea)]
- mTOR inhibitors: These include sirolimus and everolimus. MOA [Bind FK binding proteins --> inhibit mTOR which is a kinase participating in downstream signalling through IL2R which is the third signal], not nephrotoxic, impaired wound healing therefore done use immediately post transplant, sirolimus pneumonitis, sirolimus has very long half life, metabolic side effects including dyslipidaemia
- Bone health
- Bi-annual BMD, may need bisphosphonates, keep Ca/ Vit D replete
- Vascular risk factors and management
- Malignancy surveillance
- Dermatological, ensure age appropriate cancer screening is adhered to
- Rejection episodes
- SCC/BCCs
- Cushing’s syndrome
- Allograft site
- Old/current AVFs
- Examine mouth for candida and gum hypertrophy
- Gouty tophi