CLINICAL NEPHROLOGY

What is new in the treatment of proliferative lupus nephritis

 

Clinical Nephrology

Revise please the abbreviation list on:

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Q.138. What is new in the treatment of proliferative lupus nephritis?

A. Effect of rituximab(Rx.), combined é steroids & MMF for induction therapy in prol-iferative L.N. ws evaluated in “L.N. assessment é rituximab” (LUNAR) study. Ptn. é class III/IV L.N. were randomly assigned to have 4 i.v. infusions of placebo or 1.0 g Rx. at 2, 24& 26 w.. All ptn. also received MMF & steroids. Incid. of complete/partial remis-sion at one y. ws higher é rituximab as comp. é placebo (57 vs 46 %), but this diff. was not statistically significant. Rx†greater reductions in anti-DNA titers & larger improve-ements in C. levels. These data do not support the use of Rx in addition to MMF & steroids for initial induction of remission in proliferative L.N..

Q.139. Describe glomerular diseases that occur due to nonamyloid fibrillar deposits?

A. G. disease é fibrillar deposits including:[Amyloidosis, fibrillary G.N.& immunotactoid Gp.]. Other rare G. disease including:[ fibronectin Gp. & collagenofibrotic Gp.]. Whereas all amyloid fibrils are Congo-red +ve, all other forms of fibrillary deposition are ch. ch. by Congo-red -ve fibrils. Fibrillary G.N. & immunotactoid Gp. are distinguished from. each other by E/M.; fibrils ch.ch. fibrillary G.N. are† smaller & typically randomly oriented as opposed to the larger & organized fibrils of immunotactoid Gp.. L.M. for both: variable & including focal or diffuse G.N. with or without crescents, membranous pattern, M.P. & amyloid-like pattern.

Ptn. é both fibrillary & immunotactoid dis. present é signif. NRP; other findings incl.:microscopic hematuria, H.T. & R.I. tht may progress rapidly. Approximately half of the ptn. developing ESRD within 2-6 y.. Both disorders can recur in R.Tx. 👈. Immunotactoid Gp. is far less common thn fibrillary G.N.. Some ptn. é both fibrillary G.N. & immunotactoid Gp. hv or will dev. Lymphoprolif-erative diso. or other malignancy. A careful search for a lymphoproliferative dis. & other malignancies should be part of routine evaluation ofimmunotactoid Gp.

Fibrillary                         &  

immunotactoid G.  ! disease are difficult to ttt & there’re no controlled trials to guide thpy. Rituximab👈has been associated é complete or partial remission of Prot in case rep., but evidence of efficacy fr. randomized trials is not available. Ptn thpy directed é findings on L.M. (e.g. i.v. Cph & steroids for crescentic G.N., or Csp. or other reg. for those é M.N.).  Ptn. é fibrillary or immunotactoid Gp. associated é CLL, related B cell lymphomas, or other disorder may respond to therapy directed to underlying disorder. DX. or R.Tx. cn be performed é ESRD. Although recurrent disease in the graft is common, rate of progression is generally slower 👈than native kidney.

Q.140. Give short account about diabetic nephropathy (Dc Np. )?

A. Dc Np. occ. in both type 1 & 2 D.M. Risk of progression of Dc Np hs improveed é last several decades, largely due to rigorous glycemic control, more aggressive B.P. control & use of ACEI.. The 3 mj. hist. ch. in G. in Dc Np. incl.:

                            (1)  Msangial expansion.  (2)  G.B.M. thickening.  &   (3) G. sclerosis.

Diff. hist. patterns hv similar prognostic significance.  Pathogenetic processes tht contribute to Dc Np. in susceptible ptn. incl.:[G. hyperfiltration; hyperglycemia & 🠝production of AGEP, 🠝pl. prorenin activity; hypoxia-inflmm. & activeation of cytokines]. Risk factors associated é Dc Np including:[F.H. of D.M., black race, Mexican-American or Pima Indian ancestry; higher systemic B.P., evid. of hyper-filtration early in course of dis.; poor glycemic control; smoking; use of oral contraceptives. Obesity & older age] may also be risk f.. No one f. is predictive in the individual patient. Ptns é nephropathy & type1DM. almost always hv other Sn of Dc microvascular dis., such as retinopathy & neuropathy. Relationship betw. Dc Np & retinopathy is less predictable in DM. II. 2007 K/ DOQI Guidelines for DM & CKD. suggested: CKD. should be attrib. to Dc Np in most ptns é diabetes if albuminuria & Dc. retinopathy are both present; other causes of CKD should be entertained if Dc retinopathy is absent.

Prot in D.M. occurs due to G.disease other thn Dc Np., or to nephrosclerosis.   Mj. clinical clues suggested nondiabetic G. disease including: 

1)   Onset of Prot < 5 y. from onset of type 1.

2)   Acute onset of R. disease.

3)   Active urine sediment é RBCs. (espcially acanthocytes) & cellular casts

4)   Sns and/or Sms of another syst. disease;

5)   Significant decreased in G.F.R. (>30%) within 2-3 m.s of ACEI/ARBS use.  👍

 

Acanthocytes:(speculated cells é irreguler projections é varying length), usually seen é liver dis.).

Q.141.What are the treatment recommendations of diabetic nephropathy?

A. In DM.I.: ACEI, as part of anti-H.T. thpy, both lower protein excr. & slow rate of dis. progression é microalbuminuria & in those é overt Np., similar effect sn in D.M. II. é ARBs/ACEI. B.P. & Prot goals are similar to prot-einuric non-diabetic C.K.D..It’s vital to realize that these ag. slow rate of progr-ession, but don’t stop it. Other modalities also required. Most important is: maintain strict B.P. & glycemic control early é course of dis.. In add., dietary 🠋protein is beneficial in established Dc Np. & aggressive lipid lowering is likely to improve CVS outcomes. Monitor of protein excr. in CRF. by repeated measure of ur. protein- or alb.- to-Cr. ratio every few m.s, using a 1^st–morning void.

N. rate of alb. excr. is <20 mg/d. (15 µg/min); persistent alb. excr. betw. 30 & 300 mg/d. (20-200µg/min) is called microalb. & é DM (esp. DM.I.), usually indicative of Dc Np (unless there’s coexistent R. dis.). Values >300 mg/d. (200 µg/min) considered 🠊overt  Prot. Alth. these cut offs : norm-, micro- & overt  Prot help determinig risk for progression, risk of overt Dc Np. is us. rel. to alb. excr. rates at all levels. "High N." alb. excretion are also at increase risk of developing Dc Np. , esp. é retinopathy.

DM. I.: Should be screened yearly (after 1^st 5 y.) for microalb..Use of alb.-to-cr. ratio in untimed ur. sample is recommended as prefered strategy for all ptns. + s. cr. & GFR. An elevated alb.-to-cr. ratio shd be confirmed, at least 2 tests done over subsequent 3-6 m., é confirmation of Dgx. requires at least 2 of 3 +ve samples. Recommendations: DM.I. + persistent microalbuminuria🠊Strictglycemic & lipid control. ACEI shd be given é B.P. >130/80 mmHg. Ptns é lower B.P. who are not on ACEI , alb.-to-cr. ratio shd monitored at 6-12 m. intervals & ACEI begun if there ‘s  evidnce of clear rise in alb. excretion and/or B.P.. By comp., type 1+ clinically evidence diabetic R. dis., start ACEI/ARB even if B.P. is<130/80 mmHg.

Q.142. What about treatment recommendations of diabetic nephropathy in type II?

A. Screening for microalbuminuria is NOT as useful in DM.II.. It’s not as predictor of progression to overt Np. as in type 1. In maniabetesy cases, microalb. present at time of D.gx. of D.M., which reflects delayed D.gx. of D.M., but obesity & athero. may 🠊microalbuminuria. Nevertheless, microalb. is ass. é incr. risk of dev. CVS. disease, & most ptns é microalb. hv other reasons for ACEI/ARBs thpy.

Once overt Prot occur, rate of loss of GFR & deleterious effect of H.T. are equivalent to tht sn in D.M. I, sugg. similar pathogenesis. If No aggressive intervenetion:[time to progr. fr. overt Prot to ESRD in either form of DM= 6-7 y.]. Overall, faster GFR decline is ass. é ⮞higher Prot, HgA1c & systolic B.P..

Optimal initial thpy of Np in D.M.II.🠊angiotensin inhibition. Although There,re ➳ more data on renoprotective effect of ARBs, ACEI can be also be used . Since the goal B.P. in DM. & proteinuric CKD of any cause is <130/80 mmHg, almost all ptns é Dc Np. will need additional ag.. Diltiazem or verapamil 🠊further 🠟in Prot excretion🠊further protection, while loop diuretic is typically req. é edema.

Despite beneficial effect on Prot., it’s recomm. NOT using combined 🠊[ACEI +ARBs] since no reliable study has demonstrated a long term benefit effect on R. function., & there’s an increase in adverse S.E., especially mortality . 💀👽💀

Q.143. What about microalbuminuria in type 2 diabetes mellitus?

A. Def.: { Persistent ur. alb. excr. betw. 30-300 mg/d. (20-200 µg/min).}                                                                  * *  Macroalb. refers to alb. excretion >300 mg/d. (200 µg/min).

Prevelance of microalb. in DM. II., at 10 y.: betw. 25-40 %. Some ptn. hv micro-alb. at time of Dgx.: (undiagnosed D.M. or some other disease ⮞microalbumin). Microalb. in DM.II. is associated é 🠋kid. function, progression to macroalb. &🠉long-term M.R. However, remission to normoalb. may occur.. Remission f. including: [short duration of microalb., better glycemic control, better B.P. control & use of ACEI/ARBS]. The preferred screening strategy is measuring of ur. alb.-to-cr. ratio in an untimed urine sample. Value of 30-300 mg/g of Cr., suggsted: alb. excr. is betw. 30-300 mg/d. & that microalb. is probably present.

Recomm. : Urar./y. in DM.II. An increase ratio, confirmed at least 2 added tests done over subsequent 3-6 m.s, é confirmed of dgx at least 2 of 3 +ve samples. Persistent microalb. & goal B.P., we recommended: ACEI/ARB rather than other anti-H.T. Other drugs are added as necessary. Goal B.P. in D.M.is at least <140/90 mmHg & perhaps <135/85 mmHg. Data are limited é value of ttt microalb. é ACEI /ARB in DM.II. who’re normotensives, since no trials have been limited to ptns é baseline B.P. <135/85 mmHg. Given the low cost & low rate of S.E of such theapy, among normotensive ptns é microalb., ttt é ACEI or ARB rather than obs..No suff-icient data to recmm. ACEI for Iry prevention in normoalb. Normotensive D.M. II., but screened é 6-12 m. for microalb. & ACEI started é persistent microalb..

Q.144. What about dialysis in diabetic Nephropathy?

A. “Dialysis in Dc. Nephropathy”:

      Diabetes is the most common cause of ESRD in patients requiring RRT. , accounting for 45 % of cases in USA . Although less frequent in many other countries, DM is also common cause of ESRD throughout the world.

      Survival in diabetics on maintenance DX. is lower thn tht sn in non-diabetics with ESRD due to ch. Gl. Disease, H.T., or other causes of ESRD. CVS. Diseases is the most common cause of death, acc. for > one-half of cases.

      R.Tx. is ass. é incr. ptn. survival & better quality of life. We recommended: R.Tx. rather thn DX. to any diabetic é ESRD who’s eligible for a R. allograft, ideally before DX. is even initiated if possible .  ياسلام  !!! 

      Among diabetics é adequate manual dexterity & visual acuity, we offer P.D. as an option for maintenance DX. Diabetics é unstable cardiac hemodyna-mics, severe vascular dis., and/or advanced neuropathy are most often ttt.ed é in-center H.DX. Few studies have specifically analyzed efficacy of P.D. in these patients. Very few diabetics choose home HDX. which's generally ass. é relatively highest patient survival rates.

 

Q.145. How can amyloidosis (amylo) of various types affect the kidney?  

 

A. Definition: Amylo is [a group of dis. ch.ch. by extracellular deposition of amyloid fibrils]. R. involvement occ. in AL amylo.(Iry), ch.ch. by depos. of Ig. light chains, or AA (2^nd ry) amylo., ch.ch. by deposition of amyloid A. R. involvement may occ. in hereditary forms of amylo.. C.P. of R. dis. vary é site of involvement. The most comm presentation of AL & AA amylo.⮞ heavy Prot, associated é G. deposits. Ptns é vascular deposits present é slowly progr. CKD. é 👉little or no Prot.. Less commonly, ptns é tubuler deposits present é tubuler dysfunction e.g. type 1(distal) RTA. or polyuria due to nephrogenic D.I. & rarely, Fanconi syndrome. Crescentic G.N. is extremely rare. Etiology of R. amylo. depends on type. An abnormal clonal proliferation of pl. cells⮞AL amyloidosis. Ch. inflmm.  disease⮞AA amyloid-osis. Adult or juvenile rhoid arthritis is the mj. cause of AA amylo.. Other mj. causes é AA incl.:[ankylosing spondylitis, psoriatic arthritis, ch. pyogenic infection, inflmm. bowel disease, cystic fibrosis, neoplasms & FMF.]. Less commonly: genetic disorder associated é ch. inflmmation⮞AA amylo.. ttt of AL amylo. is directed at elimination of monoclonal protein & pl. cell clone which may⮞ reversal of organ dge. Factors tht influence R. resp. to therapy including: degree of baseline Prot & s. Cr.

Ptns who progress to ESRD can be ttted é either DX. or R.TX.. H.DX & CAPD app. to be equally effective. Prognosis for DX. ptn.s is not good, though somewhat better for those é AA comp. to AL amylo.. Experience é R.Tx. is mainly limited to AA amylo.. Limited data sugged: graft survival is similar but ptn survival is lower in AA amylo. compared to other forms of R. disease. Recurrent amyloid deposition in Tx.: 20-33 % occur due to continuous activity of underling disease, but graft loss due to recurence is uncommon.

146. How to evaluate a child with glomerular disease? What is most common causes of G.N. in children

A. Iry (R. dis.) & IIry (eg, autoimmune, vasculitis, or infection) disorder⮞ G. disease in children . C.P., urinalysis & rate of protein excretion divide children é G. disease into two groups : ptns é G.N. & those é N.S.. In both groups, R. function is assessed by measuring s. Cr.. Children é G.N. typically present é: [edema, H.T., reddish brown/brown colored urine & rising s. Cr.]. Urinalysis : evidence of G. bleeding, e.g. R.B.Cs & RBCs casts. Ptns usually have proteinuria >100 mg/m2/d., when there’s no gross hematuria. Further evaluation é G.N. incl. serologic testing for a recent streptococcal infection., ANA/ anti-DNA A.B., C. studies & ANCA. R. biopsy is perfered to confirm a D.gx., determine extent of R. inj., and/or predict R. outcome. Timing of biopsy depends upon clinical setting.  

Children é N.S. typically present only é edema, an inactive urine sediment (i.e, few or no R.B.Cs & cellular casts) & NRP = urinary protein excretion > 50 mg/kg/d. or  40 mg/m2/h.. Children é both nephritic & N.S. are evaluated in similarly to those é G.N., because many of G.N. also present é N.S. Whereas, idiop. N.S. doesn’t typically have an inflmm. component. Children who’re suspected of having G. disease, but do not have evidence of either G.N. or nephrotic after initial assessment, are evaluated as if they have G.N., as they're likely to have mild G.N. course.

- The most common causes of G.N. in children?   

A. Primary G.N. :

1)   Membranous G.N.

2)   Membranoproliferative G.N. type I

3)   Membranoproliferative G.N. type II (DDD.)

4)   IgA nephropathy

5)   Anti-glomerular B.M. dis..

6)   Idioapthic crscentic G.N.

Secondary G.N.:

1)   Post-streptococcal G.N.

2)   Other post-infectious G.N.

3)   Henoch-Schönlein purpura nephritis .

4)   Systemic lupus erythematosus nephritis .

5)   Microscopic Polyangiitis .

6)   Wegener Granulomatosus .

 

 

 

 

Q.147. How to use serologic testing & I.F. microscopy in diagnosis of G.N. in children?

A. Serologic testing & I.F. microscopy in diagnosis of G.N. in children: