Renal

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

Risk factors

T2DM, hypertension, analgesic consumption, gout, vasculitides, idiopathic glomerulonephritis, amyloid, sarcoid, renal vascular disease

Complications

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

Management:

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
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

Dialysis specific management

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
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
- 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
- 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

Examination

SCC/BCCs
Cushing’s syndrome
Allograft site
Old/current AVFs
Examine mouth for candida and gum hypertrophy
Gouty tophi