قراءة
عرض

Chronic kidney disease (CKD)

Dr .ALI A. ALLAWI Nephrologist and Transplant specialistInternist


Previously termed chronic renal failure, refers to an irreversible deterioration in renal function which usually develops over a period of years. Initially, it is manifest only as a biochemical abnormality but, eventually, loss of the excretory, metabolic and endocrine functions of the kidney leads to the clinical symptoms and signs of renal failure, collectively referred to as uraemia. Chronic kidney disease (CKD)

DM IS COMMENST CAUSE

HistoryParticular attention should be paid to: Duration of symptoms Drug ingestion, including non-steroidal anti-inflammatory agents, analgesic and other medications, and herbal remediesPrevious medical and surgical history, e.g. previous chemotherapy, multisystem diseases such as SLE, malaria Previous occasions on which urinalysis or measurement of urea and creatinine might have been performed, e.g. pre-employment or insurance medical examinations, new patient checksFamily history of renal disease. Clinical approach to the patient with CKD or any other form of renal disease


SymptomsThe early stages of CKD are often completely asymptomatic, despite the accumulation of numerous metabolites. Serum urea and creatinine concentrations are measured in CKD, since methods for their determination are available and a rough correlation exists between urea and creatinine concentrations and symptoms. These substances are, however, in themselves not particularly toxic.


Such metabolites must be products of protein catabolism (since dietary protein restriction may reverse symptoms associated with CKD) and many of them must be of relatively small molecular size (since haemodialysis employing membranes which allow through only relatively small molecules improves symptoms). Symptoms are common when the serum urea concentration exceeds 40 mmol/L, but many patients develop uraemic symptoms at lower levels of serum urea. Symptoms include: Loss of appetite, Malaise, loss of energy, Insomnia Nocturia and polyuria due to impaired concentrating ability Itching Nausea, vomiting and diarrhea


Paraesthesiae due to polyneuropathyRestless legs’ syndrome (overwhelming need to frequently alter position of lower limbs) Bone pain due to metabolic bone disease Paraesthesiae and tetany due to hypocalcaemia Symptoms due to salt and water retention – peripheral or pulmonary oedema Symptoms due to anaemia Amenorrhoea in women; erectile dysfunction in men. In more advanced uraemia CKD stage 5, these symptoms become more severe and CNS symptoms are common:Mental slowing, clouding of consciousness and seizures, Myoclonic twitching.Severe depression of glomerular filtration can result in oliguria. This can occur with either acute kidney injury or in the terminal stages of CKD. However, even if the GFR is profoundly depressed, failure of tubular reabsorption may lead to very high urine volumes; the urine output is therefore not a useful guide to renal function.


InvestigationsThe recommended investigations aims are:• to identify the underlying cause where possible,since this may influence the treatment• to identify reversible factors that may worsen renalfunction, such as hypertension, urinary tractobstruction, nephrotoxic drugs, and salt and waterdepletion• to screen for complications of CKD, such asanaemia and renal osteodystrophy• to screen for cardiovascular risk factors.Referral to a nephrologist is appropriate for patients with potentially treatable underlying disease and those who are likely to progress to ESRD.


Kidney Biopsy: In the patient with bilaterally small kidneys, renal biopsy is not advised because (1) it is technically difficult and has a greater likelihood of causing bleeding and other adverse consequences, (2( there is usually so much scarring that the underlying disease may not be apparent, and (3) the window of opportunity to render disease-specific therapy has passed. Other contraindications to renal biopsy include uncontrolled hypertension, active urinary tract infection, bleeding diathesis (including ongoing anticoagulation), and severe obesity. Ultrasound-guided percutaneous biopsy is the favored approach, but a surgical or laparoscopic approach can be considered, especially in the patient with a single kidney where direct visualization and control of bleeding are crucial. In the CKD patient in whom a kidney biopsy is indicated (e.g., suspicion of a concomitant or superimposed active process such as interstitial nephritis or in the face of accelerated loss of GFR), the bleeding time should be measured, and if increased, desmopressin should be administered immediately prior to the procedure.


(1)AnaemiaSeveral factors have been implicated: Erythropoietin deficiency (the most significant)Toxic effects of uraemia on marrow precursor cells and retaining of Bone marrow toxins in CKDReduced red cell survivalBone marrow fibrosis secondary to hyperparathyroidism Haematinic deficiency – iron, vitamin B12, folateReduced intake, absorption and utilisation of dietary iron Increased red-cell destruction, Abnormal red-cell membranes causing increased osmotic fragility . Increased red-cell destruction may occur during haemodialysis owing to mechanical, oxidant and thermal damage.Increased blood loss – occult gastrointestinal bleeding, blood sampling, blood loss during haemodialysis, capillary fragility, or because of platelet dysfunctionACE inhibitors (may cause anaemia in CKD, probably by interfering with the control of endogenous erythropoietin release). Complications of chronic kidney disease


Disturbances of mineral metabolism are common. The spectrum of disorders includes abnormal concentrations of serum calcium, phosphate, and magnesium and disorders of parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), and vitamin D metabolism. These abnormalities as well as other factors related to the uremic state affect the skeleton and result in the complex disorders of bone known as renal osteodystrophy; it is now recommended that this term be used exclusively to define the bone disease associated with CKD. The clinical, biochemical, and imaging abnormalities heretofore identified as correlates of renal osteodystrophy should be defined more broadly as a clinical entity or syndrome called chronic kidney disease–mineral and bone disorder (CKD-MBD). The spectrum of skeletal abnormalities seen in renal osteodystrophy includes the following : (2) chronic kidney disease–mineral and bone disorder (CKD-MBD)


■ Osteitis fibrosa, a manifestation of hyperparathyroidism characterized by increased osteoclast and osteoblast activity, peritrabecular fibrosis, and increased bone turnover.■ Osteomalacia, a manifestation of defective mineralization ofnewly formed osteoid most often caused by aluminum deposition;bone turnover is decreased.■ Adynamic bone disease (ABD), a condition characterized byabnormally low bone turnover in which both bone formation and resorption are depressed (in the absence of aluminium bone disease or overtreatment with vitamin D) is also seen.■ Osteopenia or osteoporosis.■ Combinations of these abnormalities termed mixed renalosteodystrophy.■ Other abnormalities with skeletal manifestations (e.g., chronicacidosis, β2-microglobulin amyloidosis).


Radiologically, digital subperiosteal erosions and ‘pepperpot skull’ are seen. Longstanding secondary hyperparathyroidism ultimately leads to hyperplasia of the glands with autonomous or tertiary hyperparathyroidism in which hypercalcaemia is present. Serum alkaline phosphatase concentration is raised in both secondary and tertiary hyperparathyroidism. Longstanding parathyroid hormone excess is also thought to cause increased bone density (osteosclerosis) seen particularly in the spine where alternating bands of sclerotic and porotic bone give rise to a characteristic ‘rugger jersey’ appearance on X-ray.



(3) Immune dysfunction Cellular and humoral immunity is impaired in advanced CKD and there is increased susceptibility to infections, the second most common cause of death in dialysis patients, after cardiovascular disease.(4) HaematologicalThere is an increased bleeding tendency in advanced CKD, which manifests as cutaneous ecchymoses and mucosal bleeds. Platelet function is impaired and bleeding time prolonged. Adequate dialysis partially corrects the bleeding tendency in those with severe uraemia, but these patients are at significantly increased risk of complications from all anticoagulants, including those that are required during dialysis. Anaemia is common and is due in part to reduced erythropoietin production. Haemoglobin can be as low as 5–7 g/dL in CKD stage 5, although it is often less severe or absent in patients with polycystic kidney disease.


(5) Electrolyte abnormalitiesPatients with CKD often develop electrolyte abnormalities like hyperkalemia and metabolic acidosis. Fluid retention is common in advanced CKD , Conversely, some patients with tubulo­interstitial disease can develop ‘salt­wasting’ disease and may require a high sodium and water intake, including supplements of sodium salts, to prevent fluid depletion and worsening of renal function. Acidosis is common. Although it is usually asymptomatic, it may be associated with increased tissue catabolism and decreased protein synthesis, and may exacerbate bone disease and the rate of decline in renal function.


(7) Neurological and muscle functionGeneralised myopathy may occur due to a combination of poor nutrition, hyperparathyroidism, vitamin D deficiency and disorders of electrolyte metabolism. Muscle cramps are common. The ‘restless leg syndrome’, in which the patient’s legs are jumpy during the night, may be troublesome. Symptoms may improve with the correction of anaemia by erythropoietin. Clonazepam is sometimes useful. Renal transplantation cures the problem.Both sensory and motor neuropathy can arise, presenting as paraesthesia and foot drop, respectively, but appear late during the course of CKD. They are now unusual, given the widespread availability of RRT; if present, they can often improve once dialysis is established. Asterixis, fits, tremor and myoclonus are features of severe uraemia.


Dialysis Disequilibrium Syndrome: Rapid correction of severe uraemia by haemodialysis leads to dialysis disequilibrium owing to osmotic cerebral swelling.This can be avoided by correcting uraemia gradually by use of volumetric-controlled hemodialysis machines, bicarbonate dialysate, sodium modeling, earlier recognition of uremic states, and stepped initiation of dialysis (short initial treatment times with lower blood pump speeds). In addition, short and more frequent dialysis treatments are recommended with use of small surface area dialyzers and reduced blood flow rates.Seizures: convulsions in a uraemic patient are much more commonly due to other causes such as accelerated hypertension, thrombotic thrombocytopenic purpura or drug accumulation.


The risk of cardiovascular disease is substantially increased in patients with CKD stage 3 or worse (GFR < 60 mL/min/1.73 m2) and those with proteinuria or microalbuminuria.Left ventricular hypertrophy may occur, secondary to hypertension, and may account for the increased risk of sudden death (presumed to be caused by dysrhythmias) in this patient group. Pericarditis may complicate untreated or inadequately treated ESRD and cause pericardial tamponade or constrictive pericarditis. This is common and occurs in two clinical settings:Uraemic pericarditis is a feature of severe, pre-terminal uraemia or of underdialysis. Haemorrhagic pericardial effusion and atrial arrhythmias are often associated. There is a danger of pericardial tamponade, and anticoagulants should be used with caution. Pericarditis usually resolves with intensive dialysis.Dialysis pericarditis occurs as a result of an intercurrent illness or surgery in a patient receiving apparently adequate dialysis. (8) cardiovascular disease


The underlying cause of CKD should be treated aggressively wherever possible.1)RenoprotectionThe multidrug approach to chronic nephropathies has been formalized in an international protocol below: Management of chronic kidney disease


2)Correction of complicationsHyperkalaemia : Hyperkalaemia often responds to dietary restriction of potassium intake. Drugs like ACEi/ARBs and others which cause potassium retention should be stopped. Occasionally, it may be necessary to prescribe ion-exchange resins to remove potassium in the gastrointestinal tract such as sodium polystyrene sulfonate (Kayexalate) or calcium polystyrene sulfonate (calcium resonium). Emergency treatment of severe hyperkalaemia is mandatory in CKD patients.



Acidosis: Correction of acidosis helps to correct hyperkalaemia in CKD, and may also decrease muscle catabolism. The plasma bicarbonate should be maintained above 22 mmol/L by giving sodium bicarbonate supplements (starting dose of 1 g 3 times daily, increasing as required). If the increased sodium intake induces hypertension or oedema, calcium carbonate (up to 3 g daily) may be used as an alternative, since this has the advantage of also binding dietary phosphate. Renal bone disease (CKD MBD)Treatment should be initiated with Active vitamin D metabolites (either 1­α­hydroxyvitamin D or 1,25­ dihydroxyvitamin D) in patients who are found to havehypocalcaemia or serum PTH levels more than twice the upper limit of normal. The dose should be adjusted to try to reduce PTH levels to between 2 and 4 times the upper limit of normal to avoid over­ suppression of bone turnover and adynamic bone disease, but care must be exercised in order to avoid hypercalcaemia.Hypocalcaemia and hyperphosphataemia should be treated aggressively Hyperphosphataemia should be treated by dietary restriction of foods with high phosphate content (milk, cheese, eggs and protein ­rich foods) and by the use of phosphate ­binding drugs. Various drugs are available, including calcium carbonate, aluminium hydroxide, lanthanum carbonate and polymer­based phosphate binders such as sevelamer. The aim is to maintain serum phosphate values at 1.8 mmol/L (5.6 mg/dL) or below if possible, but many of these drugs are difficult to take and compliance may be a problem.


Parathyroidectomy may be required for the treatment of tertiary hyperparathyroidism. An alternative is to employ calcimimetic agents, such as cinacalcet, which bind to the calcium ­sensing receptor and reduce PTH secretion. They have a place if parathyroidectomy is unsuccessful or not possible.Treatment of Anemia :1)correction of iron deficiency anemia 2) Erythropoiesis-Stimulating Agents such as Epoetin alpha (Eprex) , Epoetin Beta (Mircera), Darbepoetin and Peginesatide (previously called Hematide) is an EPO-mimetic peptide.


(3) Renal replacement therapy (RRT) ((= dialysis or kidney transplantation)) ; The aim of all renal replacement techniques is to mimic the excretory functions of the normal kidney, including excretion of nitrogenous wastes, maintenance of normal electrolyte concentrations, and maintenance of a normal extracellular volume. At the present time, the average eGFR at the time of initiating RRT in the UK is about 8 mL/min/1.73 m2 but there is wide variation. Since there is no evidence that early initiation of RRT improves outcome, the overall aim is to commence RRT by the time symptoms of CKD have started to appear but before serious complications have occurred.


Renal transplantation offers the best chance of long ­term survival in ESRD, and is the most cost ­effective treatment. Transplantation can restore normal kidney function and correct all the metabolic abnormalities of CKD but requires long ­term immunosuppression with its attendant risks. All patients with ESRD should be considered for transplantation, unless there are contraindications.

Dialysis

Dr .ALI A. ALLAWINephrologist and Transplant specialistInternist CABMS (NEPHROLOGY) , FICMS(NEPHROLOGY) FICMS(MEDICINE)


Basic principlesIn haemodialysis, blood from the patient is pumped through an array of semipermeable membranes (the dialyser, also called an hemofilter ), which bring the blood into close contact with dialysate, flowing countercurrent to the blood. The plasma biochemistry changes towards that of the dialysate owing to diffusion of molecules down their concentration gradients. Haemodialysis



Access for haemodialysisAdequate dialysis requires a blood flow of at least 200 mL/min. AV Fistula : The most reliable long-term way of achieving this is surgical construction of an arteriovenous fistula , using the radial or brachial artery and the cephalic vein. This results in distension of the vein and thickening (‘arterialization of veins’) of its wall, so that after 6–8 weeks large-bore needles may be inserted to take blood to and from the dialysis machine. AV Graft: In patients with poor-quality veins or arterial disease (e.g. diabetes mellitus), arteriovenous polytetrafluoroethylene (PTFE) grafts are used for access. However, these grafts have a very high incidence of thrombosis and 2-year graft patency is only 50–60%. Dipyridamole or fish oils improve graft patency but warfarin, aspirin and clopidogrel do not and are associated with a high incidence of complications.Double lumen catheter : If dialysis is needed immediately, a large-bore double lumen catheter may be inserted into a central vein usually the jugular, femoral or subclavian. The internal jugular vein route is preferred.


Haemodialysis offers the best rate of small solute clearance in AKI, as compared with other techniques such as haemofiltration, but should be started gradually becauseof the risk of confusion and convulsions due to cerebral oedema (dialysis disequilibrium). Typically, 1–2 hours of dialysis is prescribed initially but, subsequently, patients with AKI who are haemodynamically stable can be treated by 4–5 hours of haemodialysis on alternate days, or 2–3 hours every day. During dialysis, it is standard practice to anticoagulate patients with heparin but the dose may be reduced if there is a bleeding risk. Epoprostenol can be used as an alternative but carries a risk of hypotension. Haemodialysis in AKI


In CKD, vascular access for haemodialysis is gained by formation of an arteriovenous fistula, usually in the forearm, up to a year before dialysis is contemplated. After 4–6 weeks, increased pressure transmitted from the artery to the vein leading from the fistula causes distension and thickening of the vessel wall (arterialisation of vein). Large­bore dual lumen catheter can then be inserted into the vein to provide access for each haemodialysis treatment. Preservation of arm veins is thus very important in patients with progressive renal disease who may require haemodialysis in the future. Haemodialysis is usually carried out for 3–5 hours three times weekly, in an outpatient dialysis unit. The intensity and frequency of dialysis should be adjusted to achieve a reduction in urea during dialysis (urea reduction ratio) of over 65%. Most patients notice an improvement in symptoms during the first 6 weeks of treatment. Plasma urea and creatinine are lowered by each treatment but do not return to normal. Haemodialysis in CKD


This involves removal of plasma water and its dissolved constituents (e.g. urea, phosphate) by convective flow across a high-flux semipermeable membrane, and replacing it with a solution of the desired biochemical composition. Haemofiltration


Peritoneal dialysis utilizes the peritoneal membrane as a semipermeable membrane, avoiding the need for extracorporeal circulation of blood. This is a very simple technology treatment compared to haemodialysis. The principles are simple: A tube is placed into the peritoneal cavity through theanterior abdominal wall Dialysate is run into the peritoneal cavity, usually undergravity.Urea, creatinine, phosphate and other uraemic toxinspass into the dialysate down their concentrationgradients. Water (with solutes) is attracted into the peritoneal cavityby osmosis, depending on the osmolarity of the dialysate. This is determined by the glucose or polymer (icodextrin) content of the dialysate . The fluid is changed regularly to repeat the process. Peritoneal dialysis


Chronic peritoneal dialysis : requires insertion of a soft catheter, with its tip in the pelvis, exiting the peritoneal cavity in the midline and lying in a skin tunnel with an exit site in the lateral abdominal wall .This form of dialysis can be adapted in several ways. Continuous ambulatory peritoneal dialysis (CAPD):Dialysate is present within the peritoneal cavity continuously, except when dialysate is being exchanged. Dialysate exchanges are performed three to five times a day, using a sterile no-touch technique to connect 1.5–3 L bags of dialysate to the peritoneal catheter; each exchange takes 20–40 min. This is the technique most often used for maintenance peritoneal dialysis inpatients with ESKD.


Automated peritoneal dialysis (APD): also called Nightly intermittent peritoneal dialysis (NIPD). An automated device (cycler) is used to perform exchanges each night while the patient is asleep. Sometimes dialysate is left in the peritoneal cavity during the day in addition, to increase the time during which biochemical exchange is occurring. Few trials have demonstrated superiority of APD over CAPD with regard to complications such as peritonitis, fluid status and in anuric patients.Tidal dialysis: A residual volume is left within th peritoneal cavity with continuous cycling of smaller volumes in and out.



Acute Peritoneal Dialysis PrescriptionAcute peritoneal dialysis is usually performed manually but can be done with the assistance of a cycler (automated machine) . It avoids the potential problems related to vascular access (hemorrhage, air embolism, thrombosis, infection) and does not require anticoagulation. The gradual but continuous nature of the procedure results in effective removal of fluid and solute with less hemodynamic instability.Acute peritoneal dialysis is most often used in the setting of acute kidney injury(AKI ), it is also beneficial in the control of volume overload states in patients with cardiovascular compromise, such as those with congestive heart failure, and in the treatment of hypothermia or hemorrhagic pancreatitis (where peritoneal lavage may be beneficial). It is most beneficial in the treatment of hemodynamically unstable patients or patients in whom vascular access is problematic. This is the combined time required for inflow, dwell, and drain. To maximize dialysis efficiency in acute peritoneal dialysis, the exchange time most commonly used is 1 hour


Inflow time: Inflow is by gravity and usually requires about 10 minutes. It may be prolonged due to kinking of the tubing or increased inflow resistance by intra-abdominal tissues in close proximity to the catheter tip. Cold dialysate solution also results in discomfort, and for this reason, the solution should be warmed to 37°C before infusion.Dwell time: The dwell period is the time during which the total exchange volume is present in the peritoneal cavity (i.e., the time from the end of inflow to the beginning of outflow).Standard dwell period. When initiating peritoneal dialysis in acutely ill and catabolic patients, the usual dwell time is 30 minutes to achieve an exchange time of 60 minutes. With a 2-L exchange volume, 48 L of fluid will thus be exchanged daily. Outflow time: Outflow of spent dialysate is by gravity and usually requires 20-30 minutes. If outflow continues to be poor, then outflow obstruction should be managed . Pain during outflow is unusual, but localized pain may occasionally be noted at the end of a drain due to a siphoning effect of the catheter on the peritoneum.

Thank you for listening




رفعت المحاضرة من قبل: AyA Abdulkareem
المشاهدات: لقد قام 140 عضواً و 414 زائراً بقراءة هذه المحاضرة








تسجيل دخول

أو
عبر الحساب الاعتيادي
الرجاء كتابة البريد الالكتروني بشكل صحيح
الرجاء كتابة كلمة المرور
لست عضواً في موقع محاضراتي؟
اضغط هنا للتسجيل