Ultimate management in End Stage Renal Disease (ESRD) is kidney transplantation

Kidney Transplantation Image

          The kidney can be obtained from an HLAA (Human Leucocyte Associated Antigen) matched living related donor or from a cadaver (of a brain death individual). Proper evaluation and consent of living donor is mandatory before accepting the kidney for donation.

Absolute Contraindication

      1. Reversible renal disease

      2. Advanced malignancy  

      3. Active glomerulonephritis

      4. Active peptic ulcer disease

      5. Active infections

      6. Ability of conservative measures to maintain life.

      7. Oxalosis

      8. Advanced cerebro-vascular disease of IHD.

      9. Previous sensitization to donor tissue.

Relative Contraindications

        1. Age should not be > 55 years)

        2. Unsuitable bladder / urethra

        3. Iliofemoral occlusive disease

        4. Diabetes mellitus

        5. Diverticulosis

        6. Psychiatric problems

Donor selection and preparation

Living donor

           Physical examination to exclude disease.

           ABO group and HLA should be matched

          Normal renal parameters

          Selective renal arteriography to rule out presence of multiple or abnormal renal arteries.

Cadaveric donors

          Should be free from malignant diseases

          Liberal infusion with normal saline for 12 hours, preoperatively to minimize changes of acute tubular necrosis in graft kidney.

Pre transplantation Recipient Preparation

    1.     Dialysis at least 48 hours before transplant surgery.

    2.     Bowel decontamination : 48 hours prior to surgery, by oral neomycin low residue diet, and high bowel washes.

    3.     Immunosuppression : by following drugs.

             a)     Glucocorticoids (Prednisolone) 30-40 immediately prior to, or at time of, transplant surgery, continued for 2 wees, then tapered.

            b)    Azathioprine (Imuran) 1-2 mg / kg day immediately after transplantation and continued life long.

            c)     Cyclophosphamide : may substituted if hepatotoxicity or nephritis after azathioprine.

            d)    Cyclosporin – A. Reserved for cases of rejections or retransplant following earlier graft rejection.

           e)     Anti-lymphocyte globulin (ALG) and OTK₃ for rejection.

Hyperacute Rejection should be suspected from

         Pain, swelling and tenderness at the site of graft.

         Haematuria associated with albuminuria

         Significant oliguria, fever

         Sudden increase  in graft size assessed by radiography

         Withering of cortical vessels, or beading of cortical vessels on angiography.

         Renal isotope scan : showing poor uptake by renal parenchyma.

         Ultrasound showing presence of perirenal collection of urine, blood or lymph.

         Rise in serum creatinine level and decreases in creatinine clearance.

         Final confirmation is by biopsy of graft kidney.

Treatment

       Methylprednisolone 500 mg IV daily for 3-5 days.

       Antithymocyte / antilymphocyte globulin

       Cyclosporin + azathioprine + steroid, if no improvement, the graft is removed.

Complications following transplantation

  Technical complications

           i. Vascular anastomotic leak of occlusion

          ii. Ureteral anastomotic leak or occlusion

          iii. Ureteral rupture

          iv. Lymphocele

          v. Renal artery stenosis

          vi. Wound infection

Immunologic : Hyperacute, acute or chronic rejection

Medical

                  i. Acute tubular necrosis  and ARF

                  ii. Infections are to impaired host defense, pneumocytes carinii, Candida, Aspergillus, Cytomegalovirus, Mycobacteria

                  iii. Recurrence of glomerulonephritis

                  iv. Poor wound healing

                   v. steroid-psychosis

                  vi. Gastro-intestinal bleeding

                  vii. Leucopenia, thrombocytopenia

                  viii. Hypercalcemia

                   ix. Myocardial infarction & stroke

                    x. Aseptic necrosis of femur

Prognosis

        One year graft survival in HLAA matched living related homograft approaches 94% using blood transfusion protocol from haplotype matches, living related donor; one year graft survival approaches 90% with matching of the HLAA and use of multiple nonspecific blood transplantation; one year graft survival of cadaver renal transplant are at risk of dying each year. The risk of death increases if the has diabetes or systemic disease.

Renal Failure with Hemoptysis

      Good pastures syndrome

      Wegener’s granulomatosis

      Henoch-Schonlein purpura

       PAN, SLE, cryoglobulinemia

       Renal vein thrombosis with pulmonary embolism

       Acute renal failure with pulmonary oedema

       Right-sided infective endocarditis with septic pulmonary emboli and immune-complex nephritis.

       Infection-tuberculosis, legionnaires disease.

Renal Disease with Jaundice

      Haemolytic-uraemic syndrome

      Hepatorenal failure (hepatic nephropathy)

      Leptospirosis (Weil’s disease)

      Hepatitis B with nephritic syndrome

      Alcoholic cirrhosis with IgA nephropathy or renal tubular acidosis.

       Polycystic disease with congenital hepatic fibrosis

       Staffers syndrome : renal cell carcinoma with non-metastatic hepatic dysfunction (e.g. cholestasis)

        Toxic : methoxyflurane

Renal disease with small kidneys

     Chronic glomerulonephritis (symmetrically smooth)

     Chronic pyelonephritis (asymmetrically scarred)

     Post-obstructive atrophy

     Renovascular insufficiency

     Late stage of many disease causing large kidneys initially

Renal Disease with large kidneys

       Acute glomerulonephritis

       Acute interstitial nephritis

       Acute tubular (or cortical) necrosis

       Acute urate nephropathy

       Polycystic disease

       Medullary sponge kidneys

       Obstructive uropathy (hydronephrosis)

   Early stage

            Amyloidosis (+ myeloma)    

            Renal vein thrombosis

            Insulin – dependent diabetes

           Malignancy (leukemia / lymphoma, Wilms’s tumor, Gradwitz tumor)

           Miscellaneous : Acromegaly, hepatic cirrhosis, hemophilia, sickle-cell anaemia, vasculitis, radiation nephritis.

           Compensatory hypertrophy

Nocturia : Diagnosis Significance

      Prostatism

      Edematous states

       Salt-losing nephropathies, e.g.

       Analgesic nephropathy

       Medullary sponge kidneys  

       Sickle cell disease

       Polyureic states e.g.

       Diabetes mellitus; insipidus

        Primary Polydipsia

        Post – ATN

Bladder pathology

           Tumor, fibrosis, infection

           Loss or reflux inhibition e.g. multiple sclerosis

         Vesico-ureteric (double micturition in children)

Causes of papillary necrosis

      Analgesic abuse, esp., phenacetin

      Obstructive uropathy, esp., with infection

       Acute pyelonephritis, esp., in diabetes mellitus     

       Sickle cell disease

        Renal tuberculosis

        Dysproteinemia

Causes of Sterile Pyuria

        Renal tuberculosis

        Analgesic nephropathy

        Renal calculi, polycystic disease

        Urinary infection treated with chemotherapy

        Nephrotoxic drugs

        Nonspecific urethritis

       Chronic prostatitis, interstitial cystitis, herpetic urethritis

Differential diagnosis of Normoglycemic Hypercalciuria

       Idiopathic

       Medullary sponge kidneys

        Immobilization (esp.in Paget’s disease)

        Sarcoidosis

        Acromegaly, Cushing’s syndrome

        (Mild) primary hyperparathyroidism (may be definitively diagnosed by documenting elevated serum pTH and / or Urinary Cyclic Adenosine Mono-Phosphate (cAMP)

         Renal tubular acidosis

          Iatrogenic : Corticosteroids, frusemide

Disproportionate Elevation of Blood Urea and Creatinine

        Dehydration (loss of water and sodium)

        Gastrointestinal haemorrhage

        Congestive cardiac failure

        High protein intake

        Drugs : Tetracycline, Corticosteroids

        Cyclosporin A

Pathological Spectrum of Renal Tubular Dysfunction

                (X = X-linked, A = autosomal,  R =  recessive ,  D = dominant )

1.Defective tubular responsiveness to hormones

              Nephrogenic diabetes insipidus (XR : distal tubular dysfunction)

               Batters syndrome (A,R Distal)

               Ladles syndrome (AD, distal)

               Pseudohyponatremia rickets (XD, proximal)

2.Primary tubular transport defects (often associated with corresponding intestinal transport defects)

            Renal glycosuria (AD, proximal)

            Hartnup disease (AR proximal)

            Cystinuria (AR, proximal)

            Cystinosis (AR, proximal : leads to uremia and death in childhood)

             Fanconi syndrome (AR, proximal, multiple defects)

             Renal tubular acidosis type 1 (AD distal)

3.       Secondary tubular transport defects

         a) Distal tubule defects : in liver disease, Medullary sponge kidneys, infantile polycystic disease, Amphotericin B, Cyclosporin A toxicity, Lithium

         b) Proximal tubule defects : in Wilson’s disease, heavy metal poisoning, medullary cystic disease

         c) Distal and / or proximal defects in Myeloma, Sjogren’s syndrome, other auto-immune disorders. Renal transplant rejection, Long-standing hypercalciuria / anemia hypokalemia, Obstructive uropathy, Analgesic nephropathy, chronic pyelonephritis.

When to suspect Renal Tubular Acidosis

        High urine pH > 6 despite acidemia (in distal RTA) and negative urine culture.

        Hyperchloremic hypokalemic acidosis

        Normal anion gap

        Hypouricemia and hypophosphatemia (proximal TA)

        Hypercalciuria : low urinary specific gravity : polyuria : failure of urinary acidification following oral ammonium chloride 100 mg / kg (distal RTA)

        Hyperkalemia and acid urine : Hyporeninemic hypoaldosteronism in elderly diabetics or obstructive uropathy (RTA Type 4)

Spectrum of Renal Pathology in Diabetes

        Renal enlargement (in early insulin – dependent diabetes ) osmotic polyuria

        Diffuse glomerulosclerosis

        Nodular glomerulosclerosis (kimmelstiel Wilson disease – Wilson lesions) : suggests insulin-dependent diabetes

        Glycogen deposition in tubules (Armanni-Ebtein lesion)

        Interstitial nephritis

        Pyelonephritis – papillary necrosis

        Recurrent urinary tract infections

        Hyporeninemic hypoaldosteronism.